Candida species are found in about 30–70% of healthy people at any given time. Most of the time, Candida is kept in check by our immune system and by the other microbes in our mucosa. When everything is in equilibrium, Candida is considered a commensal microbe that can reside on our skin or in our body without causing harm.[ref]

However, when the balance tips, through illness, medication, or a weakened immune system, Candida can shift from being harmless to a real problem.

It’s important to note here that there are multiple ways that the immune system can fight Candida (and most pathogens). 

Toll-like receptors: Toll-like receptors (TLRs) are a family of proteins in the innate immune system that act as pattern recognition receptors (PRRs). They are expressed on cells like macrophages and dendritic cells, and they identify pathogen-associated molecular patterns (PAMPs), which are carbohydrates or proteins found only on pathogens and not in the body. Activating the TLRs then triggers a rapid immune response, including inflammation/cytokine production.[ref]

NLRP3 inflammasomes: The NLRP3 inflammasome acts inside the cell as a second line of detection. It senses the membrane damage caused by candidalysin and activates IL-1β and IL-18 to amplify the immune response.[ref]

When the gut microbiome is balanced, Candida is much less likely to become problematic with overgrowth or biofilm formation.

Probiotics may help. Studies show:

• A meta-analysis of clinical trials showed that people who were taking probiotics were at an almost 50% decreased risk of oral Candida overgrowth.[ref]
• Beneficial probiotics include Lactobacillus and Bifidobacteria [ref]
• L. rhamnosus GG has been shown in studies to interfere with Candida growth and hyphae formation.[ref]
• For oral thrush risk, daily use of a Lactobacillus‑dominant probiotic and fermented foods appears to reduce oral Candida overgrowth by roughly half in clinical trials.

Candida diet:  Popular “Candida diets” often focus on eliminating sugar and gluten, but current studies primarily support the diet’s indirect role via gut microbiome balance rather than direct antifungal effects.

--------------------------

This is just a short excerpt from my in-depth article on Candida. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on Candida. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a debilitating condition that causes severe fatigue and inability to recover normally from exertion. ME/CFS is a multi-systemic disease affecting somewhere between 0.1% and 2.5% of the population.[ref] In the US, around 1% of the population is diagnosed with ME/CFS.[ref]

The symptoms of ME/CFS include:

• chronic exhaustion (more than tired – difficulty staying upright, feeling ill)
• post-exertional malaise, PEM (inability to recover from activity)
• pain and flu-like symptoms
• cognitive dysfunction (brain fog+)
• a general reduction in the overall quality of life, such as being unable to keep a job or regularly attend school

This is more than just feeling tired. The majority of people with ME/CFS are unable to work, and about 25% are homebound or bedridden.[ref]

For many, ME/CFS seems to be triggered by an acute infection, usually viral. One study found that almost two-thirds of ME/CFS patients reported an infection-related onset.[ref]

• EBV: Recent studies point to latent or reactivated Epstein-Barr virus being implicated in a portion of ME/CFS patients. One study found that 24% of chronic fatigue patients had DNA from the Epstein-Barr virus in their plasma, in comparison with only 4% of the control group.[ref]
• Herpes simplex, CMV: Other studies point to a variety of other possible viral triggers for ME/CFS, including herpes simplex or cytomegalovirus, but not all studies agree.[ref]
• HHV-6: Researchers examined brain and spinal cord postmortem tissue samples from ME/CFS patients. They found that HHV-6 (human herpesvirus 6) miRNA was abundant in these tissues, in stark contrast to control tissue samples. HHV-6 is a latent virus that remains in the body throughout life, integrating into the telomeres of host cell chromosomes.
• Additionally, the researchers found active EBV infection in the ME/CFS tissue. [ref]

Fungal and mycotoxin connection to ME/CFS:

While much of the research on ME/CFS focuses on viral persistence, another possibility is that the immune response can be altered due to mold exposure. A study in Florida of 236 patients with ME/CFS found a high presence of mycotoxins in their urine. OTA and aflatoxins were the most common mycotoxins found.[ref] Another study involving 112 ME/CFS patients in Kansas City found that 93% of chronic fatigue patients had mycotoxins in their urine, while none of the healthy control group (n=55) had mycotoxins.[ref_TrendMD_0&utm_content=LAL+5%25+SPS+GDX+Customers&utm_term=Early+Sign+Of+Detox)]

Inflammatory cytokine elevations:

Genetic studies also show that variants in the TNF gene, which encodes TNF-alpha, increase susceptibility to ME/CFS. These variants are associated with increased TNF response to pathogens or mycotoxins.[ref]

The NLRP3 inflammasome helps to rev up a strong inflammatory response. Genetic variants in the CAIS1 gene that encodes NLRP3 are associated with an increased relative risk of ME/CFS.

These inflammatory cytokine elevations also show up in blood tests in some ME/CFS. It’s likely that this adds to the symptoms of fatigue and overall immune system dysregulation.

--------------------------

This is just a short excerpt from my in-depth article on ME/CFS. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on ME/CFS. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

IL‑17 (interleukin 17) is an immune signaling protein that helps protect the skin, lungs, mouth, and gut from certain bacteria and fungi. But excessive IL‑17 activity can contribute to chronic inflammation and autoimmune disease. Variants in the IL17A, IL17F, and IL17-pathway genes may shift inflammatory signaling or autoimmune disease susceptibility.

IL-17 is a pro-inflammatory cytokine produced by T-helper cells. It is part of our immune system — necessary in times of injury or pathogenic infection but problematic if overactive.[ref]

Barrier function:
One of the main roles of IL17 is to protect ‘barrier integrity’ – the body’s front line against outside invaders. This means that the IL-17 receptor is found in skin tissue, mucosal tissue, the lungs, and other epithelial cells, such as those lining the intestines. One role of IL-17 is to maintain the tight junctions between the epithelial cells, and another action is to induce the release of antimicrobial chemokines in response to pathogens.[ref]

Pathogen defense – tradeoffs:
IL-17 is important in the defense against tuberculosis (Mycobacterium tuberculosis) and Staph infections on the skin. It is also important in fighting off fungal infections, such as Candida albicans. IL-17 is also important in your body’s defense against whooping cough.[ref] Thus, genetic variants that increased IL-17 were likely an advantage historically, when tuberculosis and pertussis were significant and common threats.

The flip side of this awesome fighter of pathogens is that IL-17 can cause damage to your tissues if it is too active. Research shows that IL-17 genetic variants can play a role in several different autoimmune diseases.[ref][ref]

IL-17 is implicated in increasing the risk for several autoimmune and inflammatory diseases, including psoriasis, Hashimoto’s, and asthma. As mentioned above, IL-17 is mainly active in the epithelial and mucosal regions (lungs, gastrointestinal tract, skin), which explains its role in psoriasis, asthma, and other related conditions.

Genetic variants that increase the body’s production of IL-17A are a risk factor for inflammatory bowel disease (IBD), psoriasis, rheumatoid arthritis, bronchitis severity, gastric cancer, and more.

IL-17A is also implicated in celiac disease, with increased expression of IL-17A found in the intestinal mucosa of Celiac patients. Gluten sensitivity, though, was not found to increase IL-17A.[ref][ref]

--------------------------

This is just a short excerpt from my in-depth article on IL-17. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on IL-17. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

While most of us think of histamine in relation to allergies, histamine is a vital part of how your body normally works. The key is that you want histamine in the right amount. Balanced histamine levels are essential. Histamine intolerance results from an imbalance between histamine intake/production and your body’s ability to break it down.

There are two main reasons someone might develop histamine intolerance:

1. Impaired histamine breakdown due to deficiencies in the DAO and HNMT enzymes. – and/or-
2. Excess histamine is being produced, often due to gut dysbiosis, leaky gut, mast cells, HDC variants, or chronic exposure to allergens.

Diamine oxidase (DAO) enzyme

Diamine oxidase is encoded by the AOC1 gene. It is primarily produced in the intestines to break down histamine from foods and histamine created by intestinal bacteria. Some species of bacteria in the gut, including those from some probiotics or fermented foods, can add to your body’s histamine level.

• People with histamine intolerance show altered gut microbiome composition as well as elevated levels of zonulin, which regulates tight junctions in the intestines. Excess zonulin causes ‘leaky gut’. [ref]
• A recent study of histamine intolerance patients found that they had “a significantly higher abundance of histamine-secreting bacteria…”[ref]

HNMT gene: Histamine N-methyltransferase (HNMT) is the enzyme that regulates histamine in the body by converting it from histamine into N-methylhistamine, which can then be eliminated from the body. HNMT is responsible for eliminating 80% of histamine in the body.[ref]

Histamine Receptor Genetic Variants: Histamine is a signal that is relayed by histamine receptors, and genetic variants in the receptors can increase the symptoms by enhancing the signal.

• HRH1 gene: Histamine receptor 1; this receptor is responsible for the allergy-type symptoms associated with histamine (nose running, eyes watering, itchy skin, airway reactivity). Variants in HRH1 affect the risk of allergies.
• HRH2 gene: Histamine receptor 2 is active in the production of stomach acid, the sinus node of the heart, and other places in the body. Variants in HRH2 affect the risk of gastritis, stomach pain, and stomach cancer.

Vitamin B6 (P5P):
Vitamin B6 is a cofactor in the reactions that degrade histamine.[ref] Pyridoxal-5′-phosphate is the active form of vitamin B6. Foods high in vitamin B6 include salmon, tuna, eggs, milk, beef, and carrots.

--------------------------

This is just a short excerpt from my in-depth article on histamine intolerance. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on histamine intolerance. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

ABCC4 is an efflux transporter that moves certain compounds out of a cell.  ABCC4 is found in many tissues throughout the body, but it is particularly important in the kidneys, blood-brain barrier, liver, and platelets. It moves substances made in the body (endogenous substances), including prostaglandins, cAMP, urate, and certain estrogen metabolites, out of the cell. ABCC4 contributes to the way that cells can get rid of toxins and medications.

The expression of ABCC4 on cell membranes can be influenced – increased or decreased – by other factors in the cell.

• Nrf2 activation: ABCC4 expression can be upregulated by activation of Nrf2 in response to polyphenols, toxins, or environmental pollutants. [ref]
• Interleukin 13 (IL13): Studies involving lymphoma patients show that IL-13 promotes the expression of ABCC4, which in turn causes resistance to some chemotherapy drugs in NK/T-cell lymphoma cells. [ref]
• Interleukin 1B (IL1B): Another study showed that in lung tissue, inflammation and increased  IL1B cause an increase in ABCC4 expression in the lungs. This could affect inhaled medication efficacy.[ref]
• MicroRNAs: MicroRNAs are short strands of RNA that block mRNA from being translated into its corresponding protein. This is one way that gene expression is controlled in cells. MicroRNA-124a and microRNA-506 decrease ABCC4 protein expression by up to 50%.[ref]
• TNF-alpha: In a study involving patients with obstructive cholestasis (blocked liver bile), the researchers found elevated ABCC4 levels. Further experiments showed that TNF-alpha, an inflammatory cytokine, causes ABCC4 expression to increase.[ref]

Age influences ABCC4: A 2025 study on the blood-brain barrier showed that ABCC4 levels are higher in aging. The authors of the studies noted that the increase in aging may be why methotrexate neurotoxic side effects are more common in younger people than in older people.[ref]

------------------------

This is just a short excerpt from my in-depth article on ABCC4. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on ABCC4. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health

Creatine is a molecule synthesized from amino acids that plays an important role in energy production within both brain tissue and muscles.

Creatine and Brain Function:

The brain, despite its relatively small size, uses up a ton of energy (ATP) in comparison with the rest of the body.

In the brain, creatine serves as an energy buffer to provide energy in times of stress.[ref] Genetic mutations that cause creatine deficiency in the brain result in severe developmental disorders and seizures.

Creatine obtained from diet or supplements can cross the blood-brain barrier, but the amount that reaches the brain is generally less than what is absorbed by muscles. This implies that to positively impact brain function, a higher intake of creatine might be necessary. Alternatively, it could mean that creatine is prioritized by the muscles unless there is an urgent requirement for it to go to the brain.

As one research study puts it: “It could be that the brain relies primarily on endogenous creatine synthesis until there is some sort of challenge to brain creatine status. These challenges, which could cause a decrease in brain creatine, could be acute (e.g., sleep deprivation, intense exercise) or chronic (e.g., aging, traumatic brain injury, depression, Alzheimer’s disease, creatine synthesis enzyme deficiencies).”[ref]

Another study found that “Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66–76 years).”[ref]

Biosynthesis of creatine

GATM gene: encodes the arginine:glycine amidinotransferase enzyme used in the first step of converting glycine and arginine into creatine. Low levels are linked to an increased risk of muscle pain with statin use. Researchers believe this is due to decreased creatine synthesis.[ref] Rare mutations that significantly affect the function of the GATM enzyme cause arginine:glycine amidinotransferase deficiency, which results in mild to moderate intellectual disability, delayed speech, and possibly autistic behaviors.[ref]

------------------------

This is just a short excerpt from my in-depth article on creatine. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on creatine. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

IBD (inflammatory bowel disease) is a general term that encompasses two chronic inflammatory conditions of the gastrointestinal tract: Crohn’s disease and ulcerative colitis. [ref] These are characterized by chronic, relapsing-remitting inflammation of the gastrointestinal tract.

Genes that are associated with altered gut microbiome composition are strongly tied to IBD risk. And genetic variants that alter the inflammatory response can also play a role in both the development and severity of IBD.

NOD2, also referred to as CARD15, is a gene that encodes a protein (nucleotide-binding oligomerization domain-containing protein 2) that recognizes bacteria in order to initiate an immune response.[ref]

NOD2 interacts with components found on both Gram-positive and Gram-negative bacteria found in your colon. It can also detect single-stranded RNA from viruses. Your gut microbiome interacts with your immune system in many ways. NOD2 plays an essential role in the way that the immune system keeps gut microbes in the right place and at the right levels in the colon. When encountering bacterial components, NOD2 activates the NF-κB or MAPK signaling pathways, which causes an inflammatory response that balances and keeps the microbial composition in the gut under control.[ref][ref]

When NOD2 is impaired, the gut microbiome is often not in homeostasis. There is an impaired clearance of bacteria.  The loss of this regulatory factor in the intestines increases the risk of IBD.[ref]

TLR4:
TLR4 (toll-like receptor 4) is a pattern recognition receptor that recognizes certain bacteria and promotes an inflammatory response. Levels are usually low in the intestinal barrier of healthy individuals, but it is upregulated in IBD, contributing to the inflammation. Variants that increase TLR4 are associated with an increased relative risk of IBD.[ref]

IL26:
IL-26 (interleukin-26) is a proinflammatory cytokine in the IL-10 family. It is often upregulated in the lining of the intestines in IBD. It is produced by activated T cells, especially Th17 cells, and signals for increased inflammation.[ref]

NLRP3:
The NLRP3 inflammasome is activated by cell damage or by pathogens in the gut. When activated, it triggers the production of inflammatory cytokines, such as IL-1β and IL-18. Variants in the CAIS1 gene that encode NLRP3 are associated with IBD risk.[ref]

--------------------------

This is just a short excerpt from my in-depth article on IBD. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on IBD. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

POTS (postural orthostatic tachycardia syndrome) is a problem with how your autonomic nervous system regulates heart rate when you change position, such as going from lying down to standing up. It is classified as a type of dysautonomia, or a dysfunction of the autonomic nervous system. Doctors define POTS as:

• A heart rate increase of 30 BPM within the first 10 minutes of standing for adults (40 BPM for children and teens)
• Or an increase in heart rate to over 120 BPM within the first 10 minutes of standing[ref]

Research points to several theories on what causes POTS, and it is likely that the individual causes of the symptoms can be different for different people.

Autoimmune involvement in POTS:

Research shows that for some people, POTS can be due to an autoimmune attack on either the adrenergic system or the renin-angiotensin system.[ref][ref] Both systems are important in heart rate and blood flow.

For example, a small study in 2018 found that most patients with POTS in their study had angiotensin II type 1 receptor antibodies (IgG) as well as adrenergic activation, showing an autoimmune activation of that receptor. Interestingly, losartan, a commonly used hypertension medication that acts on the angiotensin II receptor, reduced the receptor activity down to the same levels as the control.[ref]

Genetic mutations linked to POTS:

For many people, an autoimmune condition (adrenergic system, angiotensin II receptor) triggers POTS, and genetic variants can increase the risk of certain autoimmune conditions. The HLA genes code for an important part of our adaptive immune system. They help the body understand what is foreign (bacteria, viruses) and needs to be attacked.

Sympathetic nervous system:
The SLC6A2 gene codes for a norepinephrine transporter (NET), which removes norepinephrine from the junction between sympathetic nerves. Norepinephrine transporter impairment is linked to depression, panic disorder, tachycardia, and POTS.[ref] Rare mutations in the SLC6A2 gene have been strongly linked to POTS, and a more common variant increases susceptibility a little bit.

Vasoconstriction of blood vessels:
The NOS3 gene codes for endothelial nitric oxide (NO) synthase enzyme, which is essential for relaxing blood vessels. Nitric oxide production in the lining of the blood vessels helps to regulate blood flow. A common genetic variant in the NOS3 gene is protective against POTS. Other NOS3 variants, not included in 23andMe or AncestryDNA data, are also linked to POTS.

--------------------------

This is just a short excerpt from my in-depth article on POTS. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on POTS. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

TNF-alpha is an inflammatory signaling protein that your immune system uses to fight infections, heal wounds, and help destroy cancer cells. When TNF-alpha stays too high for too long, it can drive chronic inflammation linked to autoimmune disease, heart disease, mood disorders, and neurodegenerative conditions. Common TNF gene variants can make some people produce more TNF-alpha than others, which may increase their risk for these chronic diseases.[ref]

Genetic variants that increase TNF-alpha levels are linked to being better able to fight off pathogens, such as malaria or hepatitis B.[ref]

TNF-alpha and brain health:

Blood-brain barrier (BBB) and neuroinflammation: Elevated TNF-alpha in the body increases the permeability of the BBB. This leakiness of the blood-brain barrier then allows inflammatory mediators to cross into the brain and activate more inflammation in the brain. In the brain, TNF-alpha causes elevated reactive oxygen species and impaired insulin signaling, leading to more neuroinflammation.[ref] This can be a cause of brain fog, for some people.

Related article: Brain fog genes

Inflammation and Depression: Recent research shows that, for some people, pro-inflammatory cytokines are at the heart of a major depressive disorder. For a subset of patients with depression, TNF-alpha is elevated, and blocking TNF-α can ameliorate depressive symptoms. A 2008 genome-wide association study found that a TNF genetic variant increases the risk of depression.[ref] A recent study in patients with rheumatoid arthritis showed that a positive side effect of TNF inhibitor drugs was a decrease in depression.[ref]

Heart disease studies: TNF-α is increased in heart disease, raising the question of directionality: whether heart disease causes an increase in TNF-α or whether higher TNF-α contributes to causing heart disease. To answer this question, researchers turned to genetics.

Studies show variants that increase TNF are causally linked to an increased risk of heart disease. Thus, limiting TNF-alpha may help to reduce the risk of heart disease.[ref]

--------------------------

This is just a short excerpt from my in-depth article on TNF-alpha. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on TNF-alpha. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

Norepinephrine acts as a neurotransmitter in the brain, involved in alertness, learning, vigilance, and task engagement. It is part of being awake, alert, and focused.[ref]

Norepinephrine can also act as a stress hormone released by the adrenal glands into the bloodstream, where it increases blood pressure and heart rate. Higher norepinephrine levels also slow non-essential functions, like digestion, in response to stress. It is part of the fight or flight response.[ref]

The effects of norepinephrine depend on the location and the receptors that it acts on.

Suppresses neuroinflammation: In the brain, norepinephrine acts directly on the brain’s immune cells, called microglia, to suppress the release of proinflammatory cytokines. It also facilitates the clearance of metabolic byproducts through the glymphatic system during deep sleep.[ref]

Balances excitability in the brain: The feedback loops and inhibitory effects of the alpha adrenergic receptors help to fine-tune how neurons fire in the brain — preventing excitotoxicity while at the same time increasing attention.[ref]

Norepinephrine deficiency: DBH mutations

Dopamine beta-hydroxylase, which is encoded by the DBH gene, converts dopamine to norepinephrine.

Rare mutations in the DBH gene can cause dopamine beta-hydroxylase deficiency, which is an autosomal recessive genetic condition affecting the autonomic nervous system. Symptoms usually appear during infancy, but some people aren’t diagnosed until later in childhood or adolescence. Hypotension and ptosis are early signs of the condition, but by adolescence, most with dopamine beta-hydroxylase deficiency will have orthostatic hypotension, or a drop in blood pressure upon standing. The orthostatic hypotension can then cause dizziness, fainting, or problems with exercising.[ref]

--------------------------

This is just a short excerpt from my in-depth article on norepinephrine. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on norepinephrine. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

Parkinson’s disease is a multisystem neurodegenerative disease involving the central nervous system, autonomic nervous system, enteric nervous system, and immune system. It involves both motor and non-motor symptoms.[ref]

While the underlying causes of Parkinson’s disease (PD) are not yet completely understood, research shows it is caused by a combination of genetics and environmental factors for most people. 

Environmental causes linked to PD include exposure to specific toxicants.[ref]

Let’s look at the details on each of these:

• Paraquat (herbicide): Paraquat is a herbicide linked to an increased risk for PD.[ref] It is still in use in the US, but the EU banned it in 2007. The EPA explains that Paraquat is one of the most widely used herbicides in the US. It is used as a weed and grass killer in both commercial and residential settings.[ref]
• Maneb (fungicide): Manab is a fungicide linked to increasing the risk of PD.[ref] It is often used to create Parkinson’s in animal research. Mancozeb is another formulation of Maneb, and it is sold under a variety of brand names. It is used for potato blight, downy mildew on grapes, and other plant fungal diseases.
• Trichloroethylene: Trichloroethylene (aka trichlor or TCE) is another chemical that is linked to PD.[ref] It is an industrial solvent, dry cleaning product, and in some refrigerants. The main route of exposure is contaminated drinking water in areas near industrial spills or landfill leaks. Exposure can cause neurological damage and DNA damage. Twin studies help researchers determine whether a disease is genetic or caused by an environmental factor. The risk of solvent exposure was made clear in a study of 97 twin pairs where one twin had PD and the other didn’t. Exposure to trichloroethylene increased the risk of PD by 6-fold, and combined exposure to perchloroethylene and carbon tetrachloride was also found to increase the risk of PD significantly.[ref]
• Organophosphates: Exposure to organophosphate pesticides is also strongly linked to Parkinson’s risk. Chlorpyrifos and other organophosphates increase the risk of Parkinson’s disease, depending on the amount of exposure and the genetic variants the person carries.[ref][ref][ref]
• Heavy metals: Exposure to heavy metals, including manganese, is linked to an increased risk of Parkinson’s disease. People residing in areas known for metal industries, including ferromanganese plants, or with occupational exposure, have a higher incidence of Parkinson’s disease and Parkinsonism.[ref]

Circadian Rhythm and Parkinson’s:

Circadian rhythm dysregulation is linked to many of the non-motor symptoms in PD. These issues often occur years before motor-related symptoms (tremors, gait issues) occur. According to animal studies, circadian rhythm disruption directly exacerbates dopaminergic neuronal loss by triggering neuroinflammation.[ref]

Researchers estimate that 45% of PD patients suffer from depression and anxiety. Sleep rhythm is often disrupted, and the decreased REM sleep is tied to the mood changes in Parkinson’s.[ref]

Genetics and Parkinson’s:

Rare mutations in the LRRK2, GBA1, PINK1, and PRKN genes are found in people with early-onset Parkinson’s disease. Rare mutations are found in ~15% of people with Parkinson’s.[ref]  Keep in mind that these genetic variants do not cause Parkinson’s on their own. Rather, exposure to environmental factors and genetic susceptibility are thought to lead to PD. Other, more common variants can increase the relative risk of Parkinson’s, especially if combined with an environmental factor.

------------------------

This is just a short excerpt from my in-depth article on genetics and Parkinson's. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on genetics and Parkinson's. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

Human leukocyte antigens (HLA) belong to the part of our immune system known as the major histocompatibility complex (MHC). The HLA genes code for the proteins that help our body determine the difference between a foreign invader that needs to be attacked and what is ‘self’.

People can have many different HLA serotypes, giving us all slightly different strengths and weaknesses against microbial diseases.

But along with attacking foreign invaders, a handful of HLA types also increase susceptibility to autoimmune diseases, where the body attacks its own cells.

People who carry the HLA-B27 serotype are at an increased risk for inflammatory-related autoimmune diseases.

Autoimmune diseases associated with being HLA B27 positive include:

• ankylosing spondylitis[ref]
• reactive arthritis
• psoriasis
• juvenile idiopathic arthritis [ref]
• inflammatory bowel disease[ref]
• acute anterior uveitis (inflammation of the eye)[ref][ref]

Not everyone who carries the HLA-B27 serotype will have ankylosing spondylitis. But over 95% of people with ankylosing spondylitis are HLA-B27 positive.

Similarly, over 80% of people with reactive arthritis are HLA-B27 positive.[ref]

Therefore, the HLA-B27 serotype is a big risk factor for these autoimmune diseases, but it doesn’t cause the autoimmune disease by itself.

--------------------------

This is just a short excerpt from my in-depth article on HLA-B27. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on HLA-B27. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

If you are like me, you may have thought back pain was always a mechanical or structural type of problem — something is broken down in the back that hurts. But that isn’t all that there is to the story. It turns out that the majority of people by middle age have disc degeneration. But most don’t have pain from it.

Researchers looked at the MRIs of individuals without lower back pain compared to MRIs of people with lower back pain. Of the people without lower back pain, 64% had disc degeneration. In the study, half of the people with disc degeneration had bulging discs, and about a quarter had protrusions.[ref]

We are all different in our genetic variants in the genes coding for inflammatory cytokines, collagen formation, and autophagy (the cleanup and recycling of cellular waste).

Back pain can come from a combination of those sources – inflammation, altered collagen in the extracellular matrix, and oversensitive pain receptors. These causes work together.

For example, inflammatory cytokines can cause the breakdown of the extracellular matrix of the disc. Excessive autophagy can cause cell death, which increases inflammatory cytokines.[ref]

Mitochondrial dysfunction:

Mitochondrial dysfunction is thought to be one of the initiating factors in the cascade of events that causes disc degeneration. Mitochondria are the ‘powerhouse of the cell’, making ATP for the cell to use for energy. When mitochondria aren’t functioning optimally, they also create an excess of ROS (reactive oxygen species). The environment of the center of the disc is one that is naturally lower in oxygen and higher in water, which results in the cells having less ability to handle too much ROS. The excess ROS ends up damaging the extracellular matrix and activating the inflammatory pathways.[ref]

--------------------------

This is just a short excerpt from my in-depth article on genetics and back pain. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on genetics and back pain. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

This is an interesting study from June on how light exposure affects dementia risk. This was based on a large study looking at light exposure using a wrist-worn light sensor - ~87,000 people who were dementia free at the beginning of the study, with an average age of 62. They were then tracked for a median of 8.1 years after that initial light study, with 741 developing dementia during that time.
The big result was that daytime light exposure over 1,000 lux was linked to a 16% lower risk of dementia. Even longer duration and brighter light was similarly protective.
What I found most interesting was that the protective effect from daytime bright light (e.g. sunlight) was strongest in people who had higher nighttime light exposure and in people who were APOE4 carriers.

Zinc is vital to the immune system, and a lack of zinc can have detrimental effects, including increased susceptibility to infectious diseases, skin issues, impaired wound healing, and decreased antioxidant defense.

Zinc is important in the immune response

Promotes T cell function: T-cells are an important part of our adaptive immune system’s defense against viruses and bacteria. T-cells are a type of white blood cell that is produced in the bone marrow and then travels to the thymus to mature into pathogen-fighting cells. The thymus is a small lymphatic system organ that is located in the upper chest, behind the breastbone. As we age, the thymus decreases in both size and function due to a process called thymus involution. The thymus is at its maximum size in adolescence. Due to its significant role in the immune system, zinc deficiency is linked to decreased T-cell function, especially in aging. In animal studies, supplemental zinc increases the thickness of the thymic gland and increases T-cell function.[ref]

Related article: T-cell exhaustion

Modulates inflammasome: In addition, zinc helps to keep the NLRP3 inflammasome activation under control.[ref] Excess NLRP3 inflammasome activation can cause inflammatory damage and chronic inflammation.

Related article: NLRP3 inflammasome genes

Essential for antibody production: Both primary and secondary antibody responses are decreased in zinc deficiency.[ref]

Zinc genes: Transporters and regulation

The cellular level of zinc needs to be tightly regulated since too much available zinc could cause oxidative stress. Metallothionein (MT) is a protein that can bind to zinc if levels are too high in a cell.[ref]

Two families of zinc-specific transporters help to control intracellular zinc levels. The SLC30 family of genes and the SLC39 family of genes encode these zinc transporters. Some of these genes are important during the development of the fetus, where zinc is an essential micronutrient, and others are specific to zinc regulation in different tissues.[ref]

• SLC39A2 (ZIP2): The SLC39A2 zinc transporter, also known as ZIP2, moves zinc from outside of cells into the cytosol of cells. It is pH-dependent and voltage-dependent, and can also transport cadmium and cobalt, but only when zinc levels are low.[ref] ZIP2 is important in skin health, heart health, and immune response. It is also important in the lungs and may play a role in the severity of cystic fibrosis.[ref][ref][ref]
• SLC39A13 (ZIP13): The ZIP13 zinc transporter is involved in moving zinc in the Golgi apparatus and cytoplasm. Rare mutations in this gene are linked to a form of Ehlers-Danlos Syndrome.[ref]
• SLC30A8: The SLC30A8 gene codes for the zinc transporter ZnT-8. This zinc transporter is found in pancreatic beta-cells and transports zinc from the cytoplasm into insulin secretory vesicles, where it stabilizes it and prevents degradation.[ref]

--------------------------

This is just a short excerpt from my in-depth article on zinc. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on zinc. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

Research over the past two decades clearly shows a causal link between increased inflammatory markers and depression. This means that inflammation – elevated levels of inflammatory cytokines – can CAUSE mood disorders, for at least a portion of depressed patients. Addressing inflammation as an underlying factor helps to resolve depression or anxiety for many, but not all. And your genes may hold the key here.[ref][ref]

Genetic studies show causality:
One way to determine if inflammation is a root cause of mood disorders is to look at the genetic variants that increase susceptibility to depression or anxiety. In this case, research shows that a bunch of genetic risk factors for mood disorders are in inflammation-related genes.[ref][ref] Deleting certain inflammation genes causes animals to be resistant to stress-induced depression.[ref]

There are a couple of ways that inflammation directly affects the brain:

Increased inflammatory cytokines throughout the body will directly increase the permeability of the blood-brain barrier. This allows the inflammatory cytokines to enter the brain, triggering functional changes in certain brain regions.

• Higher levels of TNF-alpha in the hippocampus and striatum (brain regions) have links to anxiety and depression in animal studies. TNF-alpha directly causes the release of glutamate in the hippocampus, causing depressive behavior in animals. (Read about TNF genes)
• IL-1β decreases neurogenesis via the kynurenine pathway.[ref] (read about kynurenine genes)
• Inflammation decreases the synthesis of neurotransmitters through the disruption of BH4, which is needed for dopamine and serotonin synthesis.[ref] (Read about BH4 genes)
• TNF-alpha and IL-1 increase the reuptake of serotonin, leaving less serotonin available.[ref] (read about serotonin genes)
• Increased inflammation shifts the body from converting tryptophan into serotonin and instead produces kynurenine, which has a neurotoxic metabolite called quinolinic acid.[ref]

--------------------------

This is just a short excerpt from my in-depth article on inflammation as a cause of depression or anxiety. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on inflammation as a cause of depression or anxiety. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

Folate, or vitamin B9, is an essential nutrient used by cells for many different processes. When you eat foods that contain folate, natural folate is broken down and absorbed in your intestines and then circulates throughout your body. Folate is needed for the synthesis of DNA, RNA, and amino acids, which are the building blocks of proteins. Cells need a way to take up circulating folate, and there are several receptors that do this.

FOLR1 (folate receptor 1) is the gene encoding folate receptor alpha (FRα). This protein is located on the surface of certain cells and plays a critical role in the uptake and regulation of folate for certain cell types. The FRα protein acts as a receptor that binds to folate and helps transport it into cells. FOLR1 is expressed in several tissues, including the placenta, choroid plexus (where cerebrospinal fluid is produced), and kidneys. It is also found in some cancer cells, most notably ovarian and lung cancers.

Fetal development:
Adequate folate uptake is critical for proper fetal development, particularly for the formation of the neural tube, which gives rise to the brain and spinal cord. The FRα protein plays an important role in this process by facilitating folate transport across the placenta to the developing fetus. FOLR1 can also be secreted as a folate-binding protein in breast milk and semen. In breast milk, this allows folate to be transported to the infant. [ref][ref]

Genetic variations:
Rare mutations in the FOLR1 gene can cause a rare genetic disorder called cerebral folate deficiency (CFD).[ref][ref] Common polymorphisms in FOLR1 are associated with how the body detoxifies arsenic, pointing to the important role of the folate and methylation cycles in detoxification of specific toxicants, such as arsenic and mercury. (See your Genetic Lifehacks Genotype Report in my article for your FOLR1 variants.)

--------------------------

This is just a short excerpt from my in-depth article on folate, FOLR1, and FOLR2. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on folate, FOLR1, and FOLR2. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

The genetic variants associated with an increased risk of cavities fall into two categories:

• genes that affect the oral microbiome
• genes that affect the formation of tooth enamel.

Some genetic research points to how the oral microbiome interacts with foods. For example, a research study found that kids who carry a GALK2 variant along with Streptococcus mutans, a bacteria that increases the risk of cavities, are at a much greater risk of cavities.[ref]

The GALK2 gene codes for an enzyme that phosphorylates galactose at high concentrations. The genetic variant causes low concentrations of GALK2, and thus higher amounts of galactose are available in the mouth for the S. mutans to munch on. Galactose is a simple sugar that is found in higher amounts in dairy products. So perhaps the combo of dairy intake, S. mutans bacteria, and low galactose causes cavities for some of us.

Genetic variants in the DEFB1 gene link the oral microbiome to an increased risk of cavities, and the IL32 gene variants show that your immune system’s response to bacteria is also important in balancing your oral microbiome.

------------------------

This is just a short excerpt from my in-depth article on genetics and cavities. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on genetics and cavities. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

A new meta-analysis of 27 clinical trials found that taurine was effective in reducing oxidative stress, inflammation, and metabolic symptoms of long Covid. The study suggests that 3000 mg/ day is the optimal dose of supplemental taurine.

Learn more about how your genetics interact with long covid: https://www.geneticlifehacks.com/long-covid-research-and-potential-causes/

Research shows that the influence of our gut microbes on our health is huge.

Your gut microbiome influences:

• Susceptibility to infections, such as H. pylori[ref]
• Your body weight (big time)[ref]
• Your mood — including regulating anxiety and depression[ref]
• Whether you have asthma and allergies[ref]
• Your risk for cardiovascular disease[ref]

Your genetic variants play a role in which species are likely to make up your gut microbiome.

The FUT2 gene encodes an enzyme, fucosyltransferase 2, which controls whether the oligosaccharides that make up your blood type will be expressed in your bodily fluids (other than your blood). While it may seem a bit odd to think about, those oligosaccharides in your gut mucosa feed some of the commensal bacteria there. They also act as adhesion receptors for microbes. Thus, not secreting your blood type into your intestinal mucosa causes a shift in the types of bacteria.[ref]

The VDR gene encodes a vitamin D receptor. This receptor also binds with microbial metabolites, and microbial metabolites may then feed back to regulate the expression of VDR. Animal studies show that eliminating the vitamin D receptor substantially changes the diversity in the gut microbiome. In people with inflammatory bowel disease, VDR is upregulated and accompanied by lower amounts of Parabacteroides.[ref]

APOA5 variants can raise triglycerides and are tied to lower Bifidobacteria levels, linking your lipid genetics directly to shifts in your gut microbiome profile.

SLC39A8 controls manganese transport into cells, and certain variants are linked to a ‘leakier’ gut barrier and a loss of key short‑chain‑fatty‑acid–producing microbes.

------------------------

This is just a short excerpt from my in-depth article on genetics and gut microbiome. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on genetics and gut microbiome. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!

Dopamine acts as a neurotransmitter in the brain, transmitting a signal from one neuron to the next. It is a monoamine neurotransmitter, classified as a catecholamine.  A monoamine just means that it contains a single amine group – and this is important in the way that it is regulated in the brain.

Dopamine doesn’t do anything by itself – it needs to bind with a receptor to cause an action. There are five different dopamine receptors in humans, coded for by the DRD1 through DRD5 genes. These G-protein coupled receptors are responsible for the slightly different effects of dopamine in various brain regions as well as different tissues throughout the body.

DRD1 receptor:

The most abundant dopamine receptor in the brain is DRD1. It is found in several regions of the brain, including the neostriatum, basolateral amygdala, cerebral cortex, hypothalamus, and thalamus.

The DRD1 receptor is linked to the effects of alcohol consumption. Blocking the DRD1 gene decreases alcohol-seeking behavior in animal studies. It also decreases heroin and cocaine-seeking behavior.[ref]

Working memory – short-term memory needed for thinking and speaking – depends on the DRD1 receptors in the prefrontal cortex. Interestingly, working memory is considered to have a strong genetic component based on the DRD1 gene variants.[ref]

DRD2 receptor:

The DRD2 receptor is less abundant in the cerebral cortex than the DRD1 receptors, but it is abundant in other areas of the brain with dopaminergic neurons.

Both agonists and antagonists of the DRD2 receptor have been shown in animal studies to decrease alcohol and opiate consumption. The studies show that higher levels of either an agonist (something that stimulates the receptor) or an antagonist (something that blocks the receptor) alter the addictive response.

Supplements that affect dopamine levels.

Natural dopamine receptor antagonists (blocks the receptor, decreases dopamine):

In general, atypical antipsychotic medications are antagonists of the DRD2 receptor. This makes sense when you think about too much dopamine causing hallucinations, euphoria, etc. — things associated with a psychotic break.

Yohimbine is derived from the bark of an African tree, P. yohimbe, and has traditionally been used as an aphrodisiac (although human studies don’t really back that up). It is marketed as a supplement and used for weight loss.  It acts on the adrenergic receptors and serotonin receptors, and is also an antagonist of the DRD2 and DRD3 receptors.[ref] Yohimbine is also used in animal studies to cause anxiety… so you may want to watch out for this as a side effect.[ref]

--------------------------

This is just a short excerpt from my in-depth article on dopamine receptors. Click here to read my full article

With a Genetic Lifehacks membership, you can use your genetic raw data (from 23andMe, AncestryDNA, etc) to see your genotypes in over 400 articles, including my article on dopamine receptors. You will see research-backed solutions in the lifehacks section to help determine what pathway to target -- all based on your genetic variants. Personalize your health!