Join Here   |   Log In

Fatigue: Root causes, genetics, personalized solutions

Do you constantly feel tired, even when you know you slept well? Exhausted. Drained. Unable to function.

Fatigue is a debilitating condition that plagues many people, and research now points to the root cause of fatigue: elevated inflammatory cytokines.

This article digs into the new studies showing that inflammation causes the brain to alter our behavior. Genetics research fills in the details on why and how inflammatory cytokines cause fatigue. Understanding your genetic susceptibility to fatigue may help you to target the underlying causes.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today

Fatigue has a neuroimmune root cause:

Kind of like pornography, we all recognize what fatigue is, even if it is sometimes hard to define and quantify. Fatigue is overwhelming tiredness, but not the same type of tiredness that you get from lots of physical activity or from lack of sleep. It can be temporary or long-lasting.

But what causes fatigue? Why does it last, even when you rest enough?

Understanding why you feel fatigue from a physiological standpoint may set you on the path towards conquering it.

Fatigue in the physically ill patient is one of the most common and earliest non-specific symptoms of disease and can persist long after the medical condition has resolved.[ref]

Inflammation as a (the?) cause of fatigue:

Inflammation-induced fatigue is the concept that higher levels of inflammatory cytokine production cause the feeling of fatigue, aka chronic inflammation.

Fatigue is a totally normal response to inflammation: when your immune system is kicking into higher gear, this usually means you’re sick or wounded. And when you are sick or wounded, you should want to lie down and rest.

This fatigue response to inflammation is something that all sick or hurt animals experience.

“…the behavior of sick animals and people is not a maladaptive response or the effect of debilitation, but rather an organized, evolved behavioral strategy to facilitate the role of fever in combating viral and bacterial infections.”[ref]

But what if you aren’t sick or hurt? Chronically elevated inflammatory cytokines can trigger the same pathways that cause you to feel fatigued when you’re ill.

As one study puts it: “…sickness behaviour is not an accident of chronic inflammatory diseases but an adaptive program used during immune activation. Unfortunately, this program is switched-on considerably too long, during chronic conditions, sometimes lifelong.”

Fatigue is all in your head (neuroinflammation):

Researchers have found that the brain is the “central regulator of fatigue perception”.[ref]

Inflammatory cytokines signal an inflammatory response in the body, but how do elevated cytokines impact the brain?

Elevated levels of cytokines in the body cannot easily get past the blood-brain barrier. Instead, the peripherally elevated cytokines can signal to the brain through a couple of pathways.

  • The vagal nerve passes along the ‘inflammation’ signal to the brain from the abdomen.
  • The trigeminal nerve is responsible for the brain knowing about infections in the teeth and oral cavity.
  • At high enough levels, some inflammatory cytokines can gain access to the brain through transporters at the blood-brain barrier.[ref]

Getting Specific: What is chronic inflammation?

I’ve seen inflammation written about in vague terms on almost every alternative health or natural medicine type of website. Usually, the articles encourage eating the right diet (whatever ‘right’ diet is being promoted) or buying their supplements.

I will go into a little more depth here on the specifics of the inflammatory cytokines – and then revisit all of these in the genetic variants section below.

Inflammatory cytokines elevated in fatigue:

Known causes of fatigue include elevated levels of:

  • interleukin-1α (IL-1α, IL1A gene)
  • interleukin-1β (IL-1β, IL1B gene),
  • tumor necrosis factor-α (TNF-α, TNF gene)
  • interleukin-6 (IL-6, IL6 gene).[ref]
  • interferon-gamma and kynurenine (IDO gene)

Additionally, the NLRP3 inflammasome can cause an increase in several of the inflammatory cytokines.

Interleukin 1:

Interleukin 1 is part of the innate immune response. There are two main players here: IL-1alpha (IL-1α) and IL-1beta (IL-1β).

IL-1α is released when cells die, and it is present on the surface of immune system cells such as monocytes and B cells.

IL-1β is produced only in specific immune cells, including monocytes, macrophages, and dendritic cells. When either of the IL-1 proteins binds to the IL-1 receptor, it causes a cascade of inflammatory events to happen.[ref]

Elevated IL-1 in the brain directly leads to ‘sickness behavior’, including fever and sleep. These behavior changes are due to altered dopamine synthesis via disruption of a precursor (BH4). Serotonin production can also decrease due to a shift in tryptophan to be used for kynurenine production. Reduced dopamine means that you aren’t motivated to do anything, and reduced serotonin may mean that you are less social and a little more irritable. AKA -Fatigue.

TNF-alpha:

TNF-alpha (tumor necrosis factor alpha) is a pro-inflammatory cytokine produced by macrophages, monocytes, and other cells.  When a lot of TNF-alpha is produced by a cell, it is a signal that causes the cells to undergo cell death. Great when needed to destroy a tumor cell, but too much TNF-alpha is also linked to Alzheimer’s, Parkinson’s, psoriasis, arthritis, septic shock, and COPD.[ref]

There are two sides to TNF-alpha, though. When it docks with tumor necrosis factor receptor 1 (TNFR1 receptor), it initiates a whole cascade of inflammatory events including NF-kB activation or cell death. But there are also cases when TNF-alpha acts to modulate or reduce the immune response through binding to the TNFR2 receptor.

Elevated TNF-alpha levels are thought to be causal – or at least part of the cause – in neurodegenerative disorders such as Alzheimer’s, ALS, and Parkinson’s.[ref]

TNF-alpha inhibitor drugs are available and used for several chronic diseases. Side effects are the big drawback to these drugs, such as increased infections, fungal overgrowth, and potential increased cancer risk. For example, thalidomide is a TNF-alpha-reducing drug with a wide range of side effects, including severe birth defects.[ref]

Interferon-gamma and Kynurenine:

Interferon-gamma is a pro-inflammatory cytokine that is activated to fight off viral infections. It is the body’s first line of defense against certain viruses, and you need a good response to knock out a virus.

But elevated interferon-gamma also shifts tryptophan metabolism away from serotonin/melatonin and towards the kynurenine pathway. It can result in higher levels of the neurotoxic metabolite quinolinic acid and a reduction in serotonin and melatonin.[ref]

NLRP3 inflammasome:

Activation of the NLRP3 inflammasome causes an increase in other inflammatory cytokines such as IL-1B and IL-18.  Basically, it revs up the immune response when activated by pathogens (such as viruses) or damage to cells (wounds, radiation, DNA or RNA that isn’t inside a cell where it should be, and misfolded proteins).

Chronic activation of NLRP3 is associated with atherosclerosis, MS, and diabetes.[ref][ref][ref]. Animal studies show that NLRP3 activation and its subsequent increase in IL-1B causes significantly more fatigue than without NLRP3.[ref]

Sources of chronic inflammation:

So what causes the elevation of these inflammatory cytokines all the time? Many reasons include autoimmune diseases, chronic conditions, sleep problems, stress, and exposure to environmental toxicants.

Chronic diseases and autoimmune conditions that involve chronic inflammation and fatigue include:[ref]

  • Rheumatoid arthritis, with 50% or more reporting severe fatigue[ref][ref]
  • Sjögren’s syndrome – higher IL-1 levels and fatigue[ref]
  • Diabetes – 40% reporting fatigue[ref]
  • Cancer- higher IL-1B and TNF-alpha linked to fatigue levels[ref][ref]
  • Depressive disorder
  • Multiple Sclerosis
  • Parkinson’s disease
  • Chronic liver disease[ref]
  • NAFLD[ref]
  • Inflammatory Bowel Disease[ref]
  • chronic infections[ref]

In general, many autoimmune diseases (including the ones listed above) are characterized by aberrant inflammatory cytokine activation.[ref]

Often, though, fatigue due to chronic illness is exacerbated by additional causes…

Not always a single source!

If you don’t have a ‘chronic disease’ such as those listed above, other environmental factors may play a role in constantly feeling fatigued.  While any one of these sources of inflammation (e.g., air pollution) is unlikely to cause constant fatigue, the combination of several could be.

Sleep and Circadian rhythm:
We all know that sleep is essential to overall health. But the timing of sleep also comes into play with chronic inflammation. The body’s 24-hour circadian rhythm controls when inflammatory cytokines are high and when they are low. When your circadian system is out of balance (staying up late, traveling across time zones, eating at odd hours), this can alter the rhythm and amplitude of cytokine production.[ref]

Stress and Inflammation:
We are built to respond to stressful situations periodically – running from a tiger, dealing with the death of a loved one. But repeated stresses cause an increase in pro-inflammatory cytokines, including inflammatory cytokine elevation in the areas of the brain related to fatigue and anxiety.[ref]

Air pollution:
Increased air pollution exposure, especially to fine particulates, is linked to increased inflammation and increased oxidative stress.[ref] Specifically, higher levels of fine particulates correlate to higher levels of IL-1, IL-6, and TNF-alpha in healthy young adults.[ref]

Toxicants:
Environmental exposure to toxicants is a vast topic. Some chemicals that we are exposed to daily are likely increasing oxidative stress and increasing inflammatory cytokines.[ref] But to some extent, there is an individualized response to detoxification (metabolism, elimination) of toxicants based on genetic variants in detoxification genes.

Toxicants that may cause increased oxidative stress and increased inflammatory cytokines include pesticides (organophosphates, paraquat, pyrethroids), flame retardants, metals (lead, mercury, aluminum, arsenic, manganese, cadmium, copper), plasticizers (BPA, phthalates), and PFOAs.[ref]

 Evidence showing inflammation causes fatigue:

Correlation vs. causation: Research is clear that elevated cytokine levels are found in people with fatigue, but that doesn’t necessarily prove that it is causal. The mechanism of action seems more than plausible, but let’s see what other evidence there is.

Animal studies clearly show that increasing certain cytokine levels consistently provokes fatigue-like behaviors.

Animal studies of the brain show changes that cause fatigue-like behavior:[ref]

  • Increasing TNF-alpha interferes with noradrenaline secretion in certain parts of the brain.
  • Elevated IL-1β along with IL-6 suppressed noradrenaline release.
  •  IL-2 can inhibit dopamine release from the striatum and noradrenaline release from the hypothalamus (regions of the brain).

Ok, so researchers can induce fatigue-like behavior in animals by increasing inflammation. But what about humans?

Studies show that interferon-alpha, when used as a drug to fight chronic hepatitis C, causes fatigue symptoms. Clinical trials using interferon-alpha show that a common side effect of interferon-alpha is persistent fatigue lasting more than 6-months.[ref][ref]

Endotoxin (lipopolysaccharide, LPS) exposure causes fatigue in people. A study exposed participants to low levels of endotoxin, which is a molecule found on the out membrane of some bacteria, or to placebo. The endotoxin exposure (without any bacteria) caused an immediate rise in IL-6. While this is expected in response to a bacterial infection, there was no actual infection involved. The researchers went further and did neurological tests, with the results showing a quick depression in mood along with the rise in IL-6. Additionally, in women, the neurological tests also showed “increases in social pain-related neural activity” in certain brain regions.[ref]

Research shows that inflammation also decreases neurotransmitter formation via reducing BH4 (tetrahydrobiopterin), which is needed for dopamine and serotonin production.[ref]

The other side of the equation also works: reducing inflammation causes a reduction in fatigue.

For people with rheumatoid arthritis, drugs that target inflammatory cytokines, such as anti-TNF agents, lead to a moderate improvement in fatigue scores.[ref] As one research study points out, “Fatigue in RA is prevalent, intrusive and disabling.”[ref] Thus, the reduction in an inflammatory cytokine causing a reduction in fatigue points directly to the inflammation as the cause of fatigue.


Fatigue Genotype Report:

Members: Log in to see your data below.
Not a member? Join here.
Why is this section is now only for members? Here’s why…

Member Content:

  Log In


Why join Genetic Lifehacks?

~ Membership supports Genetic Lifehack's goal of explaining the latest health and genetics research.
~ It gives you access to the full article, including the Genotype and Lifehacks sections.
~ You'll see your genetic data in the articles and reports.

Join Here


Lifehacks: Diet, natural supplements, and lifestyle changes to stop fatigue

Fatigue can be a non-specific sign that something is wrong, and you should talk with your doctor about fatigue along with any other symptoms. For example, fatigue can be an initial symptom of cancer or autoimmune disease.[ref] Push for answers as to whether there are any indications of underlying diseases.

Dietary changes to target fatigue:

Anti-inflammatory diet: 
Studies show that targeted dietary changes to reduce inflammation help fatigue in people with chronic diseases. A review sums it up: “clinical studies demonstrate that a balanced diet with whole grains high in fibers, polyphenol-rich vegetables, and omega-3 fatty acid-rich foods might be able to improve disease-related fatigue symptoms.” [ref]

While online diet gurus may argue the details of what constitutes an anti-inflammatory diet, the overarching theme is a diet that contains whole foods and not a lot of packaged, processed food.

High folate vegetable intake decreased TNF-alpha levels in women with the MTHFR C677T TT genotype.[ref]

10 Natural Supplements to target inflammation, targeted by genetic variant:

Member Content:

  Log In


Why join Genetic Lifehacks?

~ Membership supports Genetic Lifehack's goal of explaining the latest health and genetics research.
~ It gives you access to the full article, including the Genotype and Lifehacks sections.
~ You'll see your genetic data in the articles and reports.

Join Here


Related Articles and Topics:

TNF-alpha: Inflammation and Your Genes
Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, etc? Perhaps you are genetically geared towards a higher inflammatory response. Tumor necrosis factor (TNF) is an inflammatory cytokine that acts as a signaling molecule in our immune system.

L-theanine for anxiety: genetics and nature’s chill pill
L-theanine is known for reducing anxiety and promoting sleep. Discover the many benefits of l-theanine and how supplementation might work for you.

Quercetin: Scientific studies + genetic connections
Quercetin is a natural flavonoid acting as both an antioxidant and anti-inflammatory. This article focuses on the results of clinical trials involving quercetin as well as linking to specific genetic topics. By using your genetic data, you can make a more informed decision on whether quercetin is worth trying.

Depression Causes: Genetic Overview
Depression can have multiple physiological causes. This article ties together 9 separate articles on depression to simply your genetic search.

References:

Ahn, Huijeong, et al. “Methylene Blue Inhibits NLRP3, NLRC4, AIM2, and Non-Canonical Inflammasome Activation.” Scientific Reports, vol. 7, Sept. 2017, p. 12409. PubMed Central, https://doi.org/10.1038/s41598-017-12635-6.
Almeida, Celia, et al. “Biologic Interventions for Fatigue in Rheumatoid Arthritis.” The Cochrane Database of Systematic Reviews, vol. 2016, no. 6, June 2016. www.ncbi.nlm.nih.gov, https://doi.org/10.1002/14651858.CD008334.pub2.
Anderson, Faith L., et al. “Inflammasomes: An Emerging Mechanism Translating Environmental Toxicant Exposure Into Neuroinflammation in Parkinson’s Disease.” Toxicological Sciences, vol. 166, no. 1, Nov. 2018, p. 3. www.ncbi.nlm.nih.gov, https://doi.org/10.1093/toxsci/kfy219.
Bower, Julienne E. “Cancer-Related Fatigue: Mechanisms, Risk Factors, and Treatments.” Nature Reviews. Clinical Oncology, vol. 11, no. 10, Oct. 2014, p. 597. www.ncbi.nlm.nih.gov, https://doi.org/10.1038/nrclinonc.2014.127.
—. “THE ROLE OF NEURO-IMMUNE INTERACTIONS IN CANCER-RELATED FATIGUE: BIOBEHAVIORAL RISK FACTORS AND MECHANISMS.” Cancer, vol. 125, no. 3, Feb. 2019, p. 353. www.ncbi.nlm.nih.gov, https://doi.org/10.1002/cncr.31790.
Dantzer, Robert, Jason C. O’Connor, et al. “From Inflammation to Sickness and Depression: When the Immune System Subjugates the Brain.” Nature Reviews. Neuroscience, vol. 9, no. 1, Jan. 2008, p. 46. www.ncbi.nlm.nih.gov, https://doi.org/10.1038/nrn2297.
Dantzer, Robert, Cobi Johanna Heijnen, et al. “The Neuroimmune Basis of Fatigue.” Trends in Neurosciences, vol. 37, no. 1, Jan. 2014, pp. 39–46. DOI.org (Crossref), https://doi.org/10.1016/j.tins.2013.10.003.
Eisenberger, Naomi I., et al. “An FMRI Study of Cytokine-Induced Depressed Mood and Social Pain: The Role of Sex Differences.” NeuroImage, vol. 47, no. 3, Sept. 2009, p. 881. www.ncbi.nlm.nih.gov, https://doi.org/10.1016/j.neuroimage.2009.04.040.
Finsterer, Josef, and Sinda Zarrouk Mahjoub. “Fatigue in Healthy and Diseased Individuals.” The American Journal of Hospice & Palliative Care, vol. 31, no. 5, Aug. 2014, pp. 562–75. PubMed, https://doi.org/10.1177/1049909113494748.
Geenen, Rinie, and Emma Dures. “A Biopsychosocial Network Model of Fatigue in Rheumatoid Arthritis: A Systematic Review.” Rheumatology (Oxford, England), vol. 58, no. Suppl 5, Nov. 2019, p. v10. www.ncbi.nlm.nih.gov, https://doi.org/10.1093/rheumatology/kez403.
Genuis, Stephen J., and Kasie L. Kelln. “Toxicant Exposure and Bioaccumulation: A Common and Potentially Reversible Cause of Cognitive Dysfunction and Dementia.” Behavioural Neurology, vol. 2015, 2015. www.ncbi.nlm.nih.gov, https://doi.org/10.1155/2015/620143.
—. “Toxicant Exposure and Bioaccumulation: A Common and Potentially Reversible Cause of Cognitive Dysfunction and Dementia.” Behavioural Neurology, vol. 2015, 2015. www.ncbi.nlm.nih.gov, https://doi.org/10.1155/2015/620143.
Goedendorp, Martine M., et al. “Chronic Fatigue in Type 1 Diabetes: Highly Prevalent but Not Explained by Hyperglycemia or Glucose Variability.” Diabetes Care, vol. 37, no. 1, 2014, pp. 73–80. PubMed, https://doi.org/10.2337/dc13-0515.
Hahad, Omar, et al. “Ambient Air Pollution Increases the Risk of Cerebrovascular and Neuropsychiatric Disorders through Induction of Inflammation and Oxidative Stress.” International Journal of Molecular Sciences, vol. 21, no. 12, June 2020. www.ncbi.nlm.nih.gov, https://doi.org/10.3390/ijms21124306.
Haß, Ulrike, et al. “Anti-Inflammatory Diets and Fatigue.” Nutrients, vol. 11, no. 10, Oct. 2019. www.ncbi.nlm.nih.gov, https://doi.org/10.3390/nu11102315.
—. “Anti-Inflammatory Diets and Fatigue.” Nutrients, vol. 11, no. 10, Oct. 2019. www.ncbi.nlm.nih.gov, https://doi.org/10.3390/nu11102315.
Irwin, Michael R., and Mark R. Opp. “Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity.” Neuropsychopharmacology, vol. 42, no. 1, Jan. 2017, p. 129. www.ncbi.nlm.nih.gov, https://doi.org/10.1038/npp.2016.148.
Jenko, Barbara, et al. “NLRP3 and CARD8 Polymorphisms Influence Higher Disease Activity in Rheumatoid Arthritis.” Journal of Medical Biochemistry, vol. 35, no. 3, Sept. 2016, pp. 319–23. PubMed, https://doi.org/10.1515/jomb-2016-0008.
Jim, Heather S. L., et al. “Genetic Predictors of Fatigue in Prostate Cancer Patients Treated with Androgen Deprivation Therapy: Preliminary Findings.” Brain, Behavior, and Immunity, vol. 26, no. 7, Oct. 2012, pp. 1030–36. PubMed, https://doi.org/10.1016/j.bbi.2012.03.001.
Korte, S. Mechiel, and Rainer H. Straub. “Fatigue in Inflammatory Rheumatic Disorders: Pathophysiological Mechanisms.” Rheumatology (Oxford, England), vol. 58, no. Suppl 5, Nov. 2019, p. v35. www.ncbi.nlm.nih.gov, https://doi.org/10.1093/rheumatology/kez413.
Kühl, T., et al. “Validation of Inflammatory Genetic Variants Associated with Long-Term Cancer Related Fatigue in a Large Breast Cancer Cohort.” Brain, Behavior, and Immunity, vol. 73, Oct. 2018, pp. 252–60. PubMed, https://doi.org/10.1016/j.bbi.2018.05.009.
Lee, Hye Eun, et al. “Epigallocatechin-3-Gallate Prevents Acute Gout by Suppressing NLRP3 Inflammasome Activation and Mitochondrial DNA Synthesis.” Molecules, vol. 24, no. 11, June 2019, p. 2138. PubMed Central, https://doi.org/10.3390/molecules24112138.
Lee, Hye-Mi, et al. “Upregulated NLRP3 Inflammasome Activation in Patients With Type 2 Diabetes.” Diabetes, vol. 62, no. 1, Jan. 2013, pp. 194–204. PubMed Central, https://doi.org/10.2337/db12-0420.
Lisboa, Jéssica Vanessa de Carvalho, et al. “Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial.” Nutrients, vol. 12, no. 2, Jan. 2020, p. E361. PubMed, https://doi.org/10.3390/nu12020361.
Liu, Baolong, and Jiujiu Yu. “Anti-NLRP3 Inflammasome Natural Compounds: An Update.” Biomedicines, vol. 9, no. 2, Feb. 2021. www.ncbi.nlm.nih.gov, https://doi.org/10.3390/biomedicines9020136.
Liu, Ting Ting, et al. “Dihydromyricetin Ameliorates Atherosclerosis in LDL Receptor Deficient Mice.” Atherosclerosis, vol. 262, July 2017, pp. 39–50. PubMed, https://doi.org/10.1016/j.atherosclerosis.2017.05.003.
Meyers, Allison K., and Xuewei Zhu. “The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging.” Cells, vol. 9, no. 8, July 2020, p. 1808. PubMed Central, https://doi.org/10.3390/cells9081808.
Newton, Julia L. “Systemic Symptoms in Non-Alcoholic Fatty Liver Disease.” Digestive Diseases (Basel, Switzerland), vol. 28, no. 1, 2010, pp. 214–19. PubMed, https://doi.org/10.1159/000282089.
Prabhu Anand, S., et al. “Interferon Gamma Gene +874A/T Polymorphism and Intracellular Interferon Gamma Expression in Pulmonary Tuberculosis.” Cytokine, vol. 49, no. 2, Feb. 2010, pp. 130–33. PubMed, https://doi.org/10.1016/j.cyto.2009.11.009.
Roerink, Megan E., et al. “Interleukin-1 as a Mediator of Fatigue in Disease: A Narrative Review.” Journal of Neuroinflammation, vol. 14, 2017. www.ncbi.nlm.nih.gov, https://doi.org/10.1186/s12974-017-0796-7.
Russell, Alice, et al. “Persistent Fatigue Induced by Interferon-Alpha: A Novel, Inflammation-Based, Proxy Model of Chronic Fatigue Syndrome.” Psychoneuroendocrinology, vol. 100, Feb. 2019, p. 276. www.ncbi.nlm.nih.gov, https://doi.org/10.1016/j.psyneuen.2018.11.032.
—. “Persistent Fatigue Induced by Interferon-Alpha: A Novel, Inflammation-Based, Proxy Model of Chronic Fatigue Syndrome.” Psychoneuroendocrinology, vol. 100, Feb. 2019, p. 276. www.ncbi.nlm.nih.gov, https://doi.org/10.1016/j.psyneuen.2018.11.032.
Subedi, Lalita, et al. “Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases.” International Journal of Molecular Sciences, vol. 21, no. 3, Feb. 2020. www.ncbi.nlm.nih.gov, https://doi.org/10.3390/ijms21030764.
—. “Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases.” International Journal of Molecular Sciences, vol. 21, no. 3, Feb. 2020. www.ncbi.nlm.nih.gov, https://doi.org/10.3390/ijms21030764.
—. “Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases.” International Journal of Molecular Sciences, vol. 21, no. 3, Feb. 2020. www.ncbi.nlm.nih.gov, https://doi.org/10.3390/ijms21030764.
Suryavanshi, Santosh V., et al. “Cannabinoids as Key Regulators of Inflammasome Signaling: A Current Perspective.” Frontiers in Immunology, vol. 11, Jan. 2021, p. 613613. PubMed Central, https://doi.org/10.3389/fimmu.2020.613613.
Tavares, M., et al. “Tumour Necrosis Factor-Alpha (-308G/A) Promoter Polymorphism Is Associated with Ulcerative Colitis in Brazilian Patients.” International Journal of Immunogenetics, vol. 43, no. 6, Dec. 2016, pp. 376–82. PubMed, https://doi.org/10.1111/iji.12289.
Valencia, Braulio M., et al. “The Severity of the Pathogen-Induced Acute Sickness Response Is Affected by Polymorphisms in Genes of the NLRP3 Inflammasome Pathway.” Brain, Behavior, and Immunity, vol. 93, Mar. 2021, p. 186. www.ncbi.nlm.nih.gov, https://doi.org/10.1016/j.bbi.2021.01.005.
Vollmer-Conna, Uté, et al. “Cytokine Polymorphisms Have a Synergistic Effect on Severity of the Acute Sickness Response to Infection.” Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, vol. 47, no. 11, Dec. 2008, pp. 1418–25. PubMed, https://doi.org/10.1086/592967.
Yucesoy, Berran, et al. “Genetic Variants in TNFα, TGFB1, PTGS1 and PTGS2 Genes Are Associated with Diisocyanate-Induced Asthma.” Journal of Immunotoxicology, vol. 13, no. 1, 2016, pp. 119–26. PubMed, https://doi.org/10.3109/1547691X.2015.1017061.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.