Snips about SNPs: Heart attack risk – Lp(a)

check your genetic data for lp(a)

Lipoprotein(a) carries LDL cholesterol proteins. Elevated Lp(a) is a big risk factor for heart attacks, and elevated Lp(a) is mainly due to genetics.  Check your 23andMe or AncestryDNA data today to see if you carry the genetic variants linked to elevated Lp(a). If you do? Time to talk to your doctor or go get a blood test done to find out your Lp(a) level.

Check your genetic data for rs3798220  (23andMe v4, v5, AncestryDNA):

  • C/C: risk of elevated Lp(a), increased risk for heart disease – 3.7x risk of aortic stenosis [ref][ref]
  • C/T: risk of  elevated Lp(A), increased risk for heart disease, increased risk of aortic stenosis
  • T/T: normal

Check your genetic data for rs10455872 (23andMe v4, v5; AncestryDNA):

  • G/G: likely elevated Lp(a), increased risk for heart disease – 2x risk of aortic stenosis [ref][ref]
  • A/G: likely elevated Lp(A), increased risk for heart disease
  • A/A: normal

Want more details? Check out the full article on lipoprotein(a).

*SNP stands for Single Nucleotide Polymorphism, which is when one of the nucleotide bases (the A, C, G, or Ts) is replaced by a different nucleotide base in a gene.  Want to know more about your genes? Read through all the Snips about SNPs

 

Snips about SNPs: Hangry Gene

Ever wonder how your friends can go all day without eating — or why they love intermittent fasting — when you get so irritable and grumpy?  Perhaps you have the “Hangry Gene”. Or, more accurately, perhaps you carry a genetic variant in the GNB3 gene that is linked to irritability and a bad mood when fasting.

Check your genetic data for rs5443 (23andMe v4, v5; AncestryDNA):

  • C/C: best mood, least hunger
  • C/T: somewhere in the middle with more hunger than C/C
  • T/T: worst mood, most hunger when fasting – hangry [ref]

Want more details? Check out the full article on fasting.

*SNP stands for Single Nucleotide Polymorphism, which is when one of the nucleotide bases (the A, C, G, or Ts) is replaced by a different nucleotide base in a gene.  Want to know more about your genes? Read through all the Snips about SNPs

Snips about SNPs: Alcohol Flush

Does your face flush after a drink or two? The ALDH gene is responsible for the enzyme that breaks down acetaldehyde, which is a toxin that your body produces from alcohol.

While most people can get rid of acetaldehyde fairly quickly, for some, a genetic variant in the ALDH gene causes it to build up. This can cause your face to flush — known as an alcohol flush reaction. It also can make you feel bad when drinking…

Check your genetic data for rs671 (23andMe v4, v5; AncestryDNA):

  • A/A: Alcohol flush reaction[ref], also, higher risk of lung cancer from smoking[ref]
  • A/G: Alcohol flush reaction
  • G/G: normal acetaldehyde metabolism

Want more details? Check out the full article on your alcohol drinking gene.

*SNP stands for Single Nucleotide Polymorphism, which is when one of the nucleotide bases (the A, C, G, or Ts) is replaced by a different nucleotide base in a gene.  Want to know more about your genes? Read through all the Snips about SNPs

Snips about SNPs: HFE gene and iron

The HFE gene controls how much iron you absorb in the intestines from food.  Iron is tightly regulated by the body. It is completely essential for carrying oxygen in the bloodstream and for many other reactions in the body.  But too much iron is a big problem since it is very reactive — think about how quickly iron things rust when left outside.

A couple of mutations in the HFE gene increase the amount of iron absorbed from food. This causes increased iron storage in various tissues in the body. Eventually, this can lead to hemochromatosis, or iron overload. Symptoms of too much iron can include joint pain (often moving from joint to joint) and fatigue. Hemochromatosis can involve organ dysfunction as iron gets stored in the liver, pancreas, heart, skin, and brain.

Check your genetic data for rs1800562 (23andMe v4, v5; AncestryDNA):

  • A/A: most common cause of hereditary hemochromatosis, highest ferritin levels (two copies of C282Y)
  • A/G: increased ferritin levels, can cause hemochromatosis, more of a problem if also carrying rs1799945 – C/G or G/G (below)
  • G/G: normal

Check your genetic data for rs1799945 (23andMe v4, v5; AncestryDNA):

  • G/G: can cause mild hemochromatosis, increased ferritin levels (two copies of H63D)
  • C/G: somewhat higher ferritin levels
  • C/C: normal

 

Want more details?  If you have either of the genetic variants above, get further information by reading the full article on iron overload — or talk to your doctor.

 

*SNP stands for Single Nucleotide Polymorphism, which is when one of the nucleotide bases (the A, C, G, or Ts) is replaced by a different nucleotide base in a gene.  Want to know more about your genes? Read through all the Snips about SNPs

Snips about SNPs: BCMO1 and beta-carotene

The BCMO1 gene is responsible for the enzyme that converts beta-carotene into the active form of vitamin A that your body needs.  SNPs in this gene cause it to not function as well, possibly leaving you deficient in vitamin A.

These two SNPs add together to impair your ability to convert beta-carotene.

People with a T allele on both rs12934922 and rs7501331 have a 69% decreased conversion of beta-carotene to retinol.  For people with only a single T in the rs7501331 SNP, the conversion is decreased by 32%. [ref]

Check your genetic data for rs7501331 (23andMe v.4 and v.5, AncestryDNA):

  • C/C: normal
  • C/T: decreased beta-carotene conversion
  • T/T: decreased beta-carotene conversion

Check your genetic data for rs12934922 (23andMe v.4 and v.5):

  • A/A: normal
  • A/T: decreased beta-carotene conversion
  • T/T: decreased beta-carotene conversion

 

Want more details? Check out the full article on the BCMO1 gene.

*SNP stands for Single Nucleotide Polymorphism, which is when one of the nucleotide bases (the A, C, G, or Ts) is replaced by a different nucleotide base in a gene.  Want to know more about your genes? Read through all the Snips about SNPs

Snips about SNPs: FTO and your weight

The FTO gene has the unfortunate nickname of the ‘fatso gene’ because several FTO variants are associated with obesity.  Lots of studies link it to being likely to have a higher BMI.  [ref][ref]

Of course, this SNP isn’t entirely to blame if you have weight problems. Your dietary choices, activity level, and other genetic variants also come into play. One study showed that this FTO SNP is associated with an average increase in weight of 7lbs. Another study linked it to an increase of 1.4 to 2.8 BMI points.[ref][ref]

Check your genetic data for rs9939609 (23andMe v4, v5; AncestryDNA)

  • A/A: higher risk of obesity, increased BMI
  • A/T: increased risk of obesity, increased BMI
  • T/T: normal

 

Want to know more? Get all the details in the full article on the FTO gene.

 

*SNP stands for Single Nucleotide Polymorphism, which is when one of the nucleotide bases (the A, C, G, or Ts) is replaced by a different nucleotide base in a gene.  Want to know more about your genes? Read through all the Snips about SNPs

Hacking your migraines: solutions personalized for you

Migraine plague more than a billion people worldwide;  women are affected three times more often than men. [ref] That is a lot of people who know the pain, mental fogginess, sensitivity to light, and overwhelming desire to crawl into a dark hole and hide from the world.

Migraines: Symptoms, causes, research, and genetics

Migraine symptoms generally include:

  • headache (usually lasting 4 to 72 hours)
  • nausea and possibly vomiting
  • hypersensitivity to light, sounds, smells
  • sensory disturbances, aura (sometimes)

Somehow that list of symptoms doesn’t really do a migraine justice. For me, migraines are more than a headache — and usually, the pain isn’t even the worst part. Instead, the altered ability to think is what really gets to me. Usually, I’m fuzzy-headed, irritable, somewhat nauseous, and often cold (or hot).  My reflexes are slow, I can’t see right, and I am completely unable to do math  (try multiplying something the next time you have a migraine… maybe it is just me!).

There are a couple of different types of migraines:

  • migraine with aura – about 1/3 of people get auras
  • migraine without aura
  • hemiplegic migraines (rare, numbness/tingling on one side of the body)

Some people get premonitory or prodromal symptoms – these symptoms can occur up to a day or two prior to the migraine. Premonitory symptoms can include irritability, fatigue, food cravings, stiff neck, sensitivity to sounds, and yawning. On a PET scan, these symptoms are shown to accompany an increased blood flow to the hypothalamus. [ref]

Chronic migraines affect around 2% of the population. The condition is differentiated from regular migraines if a person is plagued by migraines at least 8 days per month and headaches at least 15 days per month.  [ref] 

What is going on in your brain when you have a migraine?

In the 1960s, researchers found that people with migraines have higher levels of a serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in their urine. This prompted a lot of research over the past five decades into the relation between the serotonergic system and migraines. More recently, researchers have also investigated how CFRP, neuroinflammation, and altered ion levels impact migraines. [ref]

Long story short, research provides a lot of competing theories but no simple answers. 

Migraines are often described as an excitatory state in the brain – also known as a state of hypersynchrony. Other researchers describe migraines as the brain over-responding to stimulus. [ref]

The research can be broken down into three paths:

  • vascular causes (intracranial constriction and vasodilation)
  • neural events (hyperexcitability and cortical spreading depression)
  • nociceptive causes (pain pathways, activation of the trigeminal nerve, neuropeptides)

Serotonin in migraines:

Part of what is happening in your brain during a migraine is thought to be vasodilation – or the increase in the size of the blood vessels in your brain.  This causes decreased blood pressure. Vasodilation is thought to be a reaction to an initial period of vasoconstriction; however, the blood vessels inside the cranium don’t always act in the same manner as the rest of the body. [ref]

These vascular causes may be due, at least in part, to serotonin signaling.

Serotonin (5-hydroxytryptamine, 5-HTP) is a neurotransmitter that causes the signal to flow from one neuron to the next.  It is found in abundance in both the digestive system and the brain.

Brain morphology, the way the neurons in the brain are shaped and formed, is also affected by serotonin. There are different serotonin receptors found throughout the brain and intestinal tract that cause the diverse effects of serotonin. [ref]

Genetic studies show a link between migraine susceptibility and a type of genetic variant known as a variable number tandem repeat in the serotonin gene. [ref]

One big link between migraines and serotonin is that triptans, the most commonly used migraine prescription medication, work by amplifying the serotonin signal. Triptans act on the serotonin receptors (5-HT1B) in the blood vessels of the brain, constricting them and inhibiting the release of neuropeptides. [ref]

Using PET scans on people who had been migraine free for at least 48 hours, researchers have begun studying the 5-HT1B (serotonin) receptor in the brain. These scans showed that migraine patients have lower 5-HT1B binding than people without migraines. One caveat the study makes is that the lower serotonin receptors may either be contributing to the cause of migraines or be decreased over time as a result of repeated exposure to migraines. [ref]

Researchers have also found melatonin levels are lower in people with chronic migraine when compared to a control population. This is notable especially because serotonin is needed for the reaction in the pineal gland that produces melatonin. [ref]

One review that considers the role of serotonin in migraines found that the data supports the idea that serotonin levels are low between migraine attacks, but are shown to increase at the beginning of a migraine. This initial surge of serotonin causes vasoconstriction and is thought to be part of the aura phase. When serotonin is then broken down (which happens pretty quickly), the levels drop causing vasodilation and headache pain. [ref]

CGRP in migraines:

Another key player in vasodilation during a migraine is the vasodilator CGRP.  CGRP stands for calcitonin gene-related peptide and is released from the trigeminovascular system.

The trigeminovascular system includes both the trigeminal nerve neurons and the cerebral blood vessels. The trigeminal nerve is the largest cranial nerve. It branches to the eyes and the jaw.

Time for a picture:

Trigeminal nerve illustration. (Public domain)

Notice how the trigeminal nerve goes to the root of the teeth…  my teeth often hurt during a migraine.

These sensory nerve fibers of the trigeminal nerve can activate the release of neuropeptides CGRP, substance P, and neurokinin A. CGRP is a potent vasodilator making it important for both migraines and normal blood pressure regulation in the body. It is also thought to influence the pain portion of the migraine.[ref][ref]

Mast cells and neuroinflammation in migraines:

The release of CGRP is then thought to activate receptors on a number of different cell types including mast cells. These mast cells degranulate, releasing histamine and pro-inflammatory compounds. This degranulation of mast cells causes a “prolonged state of excitation in meningeal nociceptors”. The meninges is the lining of the skull, and nociceptors are pain receptors.[ref][ref]

Here is an image of the meninges, which includes three layers surrounding the brain (dura mater, arachnoid, and pia mater).

The brain itself doesn’t have pain receptors, but there are pain receptors and blood vessels throughout the meninges

Let’s return to what mast cells are and how they can cause problems in migraines...

Mast cells are part of the body’s immune system and are found in all of our body tissues. They stand ready to release a payload of histamine, serotonin, and inflammatory cytokines when activated by a pathogen, allergic reaction, or other signaling molecules such as CGRP. [ref]

Some researchers theorize that mast cells and neuroinflammation are at the root of migraine pathology. Histamine, which is released when mast cells degranulate, is found in elevated amounts during migraine attacks.[ref] Tryptase is also released in degranulation and is thought to sensitize pain receptors.[ref]

Other researchers theorize that central sensitization is at the root of migraines. Central sensitization involves enhanced signaling through pain pathways and is caused by overexcited pain receptors and decreased inhibition. This term is applied to various pain-related conditions such as peripheral neuropathy, IBS, and migraines.[ref]

Altered sodium, potassium, and ion levels in migraines:

Another observation of researchers is that ion levels are often altered in migraineurs. Sodium, potassium, calcium, and chloride are integral parts of how neurons fire. Neurons send signals to other neurons by transmitting electrical impulses that are carried by positive and negative ions.

How the electrical impulse travels the length of the neuron through sodium and potassium gated ion channels opening and closing. (Image By Laurentaylorj – Own work, CC BY-SA 3.0)

A recent study found that sodium (Na) levels are higher in the cerebral spinal fluid (CSF) of people with migraines compared with a control group. This backs up previous work that also showed an increase in CSF sodium levels during the course of a migraine. The other ion levels – calcium, potassium, and magnesium – did not change, nor did the sodium levels in the plasma. [ref][ref]

There have been large studies trying to determine if sodium intake affects migraine risk. One study found that for women with low BMI and men at any BMI, a low intake of sodium slightly increased the risk of headaches and migraines. [ref]

Another study found that people who have migraines have lower magnesium levels, on average, than a healthy control group. [ref]

What causes the aura in migraines?

A migraine aura is the altered sensory perception that migraine sufferers experience. These include visual alterations like sparkles and waviness of images. The Mayo Clinic explains that “A visual aura is like an electrical or chemical wave that moves across the visual cortex of your brain. The visual cortex is the part of your brain that processes visual signals. As the wave spreads, you might have visual hallucinations.”  Sensory auras may also cause tingling and problems with speaking.

The aura is thought to be a result of cortical spreading depression (CSD). CSD is a massive depolarization of neurons that occurs in the brain. A wave of hyperexcitability of the neurons is followed by a wave of inhibition.  This depolarization causes the release of potassium, hydrogen, nitric oxide, and glutamate ions as well as arachidonic acid. [ref]

Here is a visual:

Cortical spreading depression. Creative Commons Image.

This cortical spreading depression causes the pain receptors in the meninges to start firing after a bit of a delay. This firing of the pain receptors continues for a long while. Animal studies show that inducing CSD by various different means caused the pain receptors to start firing about 14 minutes later. [ref]

 

Tying this all together:

We have involvement of the serotonin system that can cause changes in blood vessel dilation. The trigeminal neurovascular system releases CGRP, which is a vasodilator that also acts on mast cells. This causes sterile neuroinflammation. Mast cells release histamine, tryptase, and other inflammatory cytokines. This is acting on the meninges, the lining of the cranium, causing pain. If the migraine is preceded by an aura, the cortical spreading depression may be what is triggering the nociceptors (pain receptors) in the meninges to fire.

What triggers migraines?

People often identify various triggers for their migraines. Traveling, foods, stress, hormones, odors, sleep deprivation, and flashing/bright lights often top the list.

One problem with identifying migraine triggers is that the premonitory or prodromal symptoms  (up to a day or two ahead of the migraine) may overlap with what people identify as triggers. Food cravings are one prodromal symptom, and various food triggers are often blamed. Altered sleep patterns are another thing identified as a trigger but could be a prodromal symptom. Bright light sensitivity could also fall into this conundrum.

Which foods trigger migraines?

That said, a lot of people have identified specific foods as being likely to cause migraines for them. Some of these include gluten, wine, cheese, and chocolate. (Read more about tyramines increasing blood pressure and genes related to histamine intolerance.) Other top triggers for migraines include MSG and beer. [ref][ref]

Studies show, though, that overall dietary patterns don’t relate to migraine risk. One study did show that women with migraines eat a slightly higher amount of fat and very slightly lower amount of protein on average. [ref][ref]

Why do scents trigger migraines?

Some people are sensitive to odors and find that certain smells (floral, perfumes, strong cleaning chemicals, paint, gasoline, plastics) can trigger migraines. [ref]

This isn’t just all in your head (pun intended). A small study looked at cerebral blood flow in people with migraines vs a control group. The migraineurs had altered blood flow in certain areas of the brain when stimulated with odors. [ref]

What causes menstrual migraines?

One really common migraine trigger for many women is the change in estrogen levels around the time of their period or during ovulation.  Migraines often go away for these women during pregnancy and after menopause.

Mast cells have estrogen and progesterone receptors, and the fluctuation of estrogen can cause mast cell degeneration and the subsequent migraine pain.

Which medications work for migraines?

Migraine drug classifications include triptans, ergotamines, CGRP monoclonal antibodies, and botox.  One thing to note about these trials on preventative medications is that most are investigating an endpoint that represents a 50% reduction in migraine frequency. If you normally have 6 days of migraines per month, a medication is considered effective if it reduces migraines to 3 days/month. So, the goal of these medications seems to be a reduction in frequency rather than actually eliminating migraines.

Ergotamines:

Ergotamines were originally derived from ergot, a fungus that infects rye and other grains. Ergot is famous for outbreaks in the Middle Ages causing what was known as St. Anthony’s fire. Ingesting grains infected with the fungus caused extreme vasoconstriction, causing a severe burning sensation in the limbs. Ergots also affect neurotransmission and cause hallucinations.

Ergotamines are available in prescription form for migraine attacks. They bind to the serotonin receptors, causing vasoconstriction as well as other effects. [ref] Migergot is one brand name that combines ergot with caffeine.  There are possible serious side effects (black box warning).

Triptans:

Triptans are often the first line of prescription medication offered to people with migraines. They target specific serotonin receptors in the brain (5HT1B, 5HT1D). These receptors are located in the trigeminal nerve endings, so it is thought that activating them prevents the release of CGPG and substance P. Triptans are used as prophylactics to prevent migraine attacks.[ref]

How well do triptans work? They seem to work better for some people than others.

A meta-analysis of 133 randomized controlled trials looked at the efficacy of triptan medications for migraines.  The conclusion was “most triptans are associated with equal or better outcomes compared with NSAIDs, ASA, and acetaminophen”.  Looking at the data, triptans relieved pain in two hours for between 42 and 76% of patients. NSAIDs, aspirin (ASA), and acetaminophen (Tylenol) relieved pain in two hours for 46 – 52% of patients. [ref]

What the meta-analysis showing that triptans and aspirin/NSAIDs are about equivalent doesn’t tell us is whether those ~50% of people that triptans work for are the same people that aspirin/NSAIDs work for… In other words, if aspirin/NSAIDs don’t work for you, would triptans be a better option? Or are 50% of the people just kind of screwed when it comes to effective medications?

Another study comparing naproxen sodium (Aleve, OTC headache medicine) with a combo naproxen sodium along with a triptan (Treximet, prescription med) found that only naproxen sodium was statistically significant in the reduction of migraines and Treximet was not. The current cost of Treximet is well over $200 for 9 tablets [source]. 43% of subjects who just took Aleve for migraine had a 50% reduction in migraine frequency (compared to 17% with the expensive prescription med). [ref]

CGRP receptor inhibitors:

Several small molecule GCRP inhibitors have been tested and are in current clinical trials for migraine usage.  They are generally termed ‘gepants’.

A new monoclonal antibody that targets CGRP, fremanezumab, was tested in a group of over 700 study participants.  The injection of fremanezumab once a month reduced migraine frequency from 9 per month to 5 per month. This was compared with placebo which reduced migraine frequency from 9 per month to 6.5 per month. [ref]

Botox:

OnabotulinumtoxinA, often called Botox, is a neurotoxin that is injected into the face. It has been approved for use as a preventative for chronic migraines.

The PREEMPT study that was the initial phase III clinical trial showed a statistical decrease in migraine-free days, going from 8.4 migraine days to 6.6 days per month on average.  [ref]

One study compared botox injections to amitriptyline, a tricyclic antidepressant used for migraines. The results showed that both were about equally effective, with around 70% of trial participants have a reduction in the number of days of migraines each month. [ref]

 


What can genetics tell you about the root cause of your migraines?

There are several ways to approach a medical problem:

  • The most common is to look at the symptoms and manage them with a pill. (migraine – pain medicine)
  • Another option is to figure out what leads up to the medical problem. (migraine – triggers such as red wine, hormone changes)
  • Researchers can look at what metabolites are changed or altered in the blood. (hard to get live samples from the brain / central nervous system)
  • Geneticist look at which genetic variants are found in people with the medical condition. This can show which genetic variants are linked to an increased risk of a disease — and shed some light on the underlying cause.

There are quite a few different gene variants that have been associated in studies with either an increased or decreased risk of migraines.  Below are a few of these variants that are commonly included in 23 and Me or AncestryDNA testing. This isn’t the whole picture, but it does cover quite a few of the variants involved in migraine risk.

Migraines are estimated to be about 50% due to heredity factors that combine with environmental factors to cause migraines. [ref][ref]

How do you use this info? Identifying the genetic variants you carry that influence migraine susceptibility may help you figure out how you get migraines and, hopefully, which migraine ‘lifehacks’ will be most effective for you.

Pain Receptors Genes Associated with Migraines:

TRPM8 gene: codes for the cold and menthol receptor. When skin temperatures decrease by 15 degrees C, it hurts due to the activation of this pain receptor. [ref]

Check your genetic data for rs10166942 (23andMe v4, v5; AncestryDNA):

  • C/C: decreased risk of migraines [ref][ref]
  • C/T: slightly decreased risk of migraines
  • T/T: higher risk of migraines, less sensitive to cold[ref]

CGRP Pathway Genes Associated with Migraines:

CGRP and brain-derived neurotrophic factor (BDNF) are coexpressed on the trigeminal nerve terminals.[ref]

BDNF Gene: codes for brain-derived neurotrophic factor

Check your genetic data for rs6265 (23andMe v4, v5; AncestryDNA):

  • T/T:  increase in risk of migraines [ref]
  • C/T: slight increase in risk of migraines
  • C/C: normal risk of migraines

MMP16 gene: Several genome-wide association studies that looked at large population groups have found that a genetic variant in chromosome 8 near the MMP16 gene is consistently associated with a reduced risk of migraines (without aura). The MMP16 gene codes for an enzyme involved in the breakdown of the extracellular matrix and tissue remodeling.

Check your genetic data for rs10504861 (23andMe v4, v5; AncestryDNA):

  • C/C: normal migraine risk
  • C/T: reduced risk of migraine
  • T/T: reduced risk of migraine [ref][ref]

 

Methylation Pathway Genes Associated with Migraines:

NNMT gene: The nicotinamide-N-methyltransferase (NNMT) gene codes for an enzyme that transfers a methyl group from SAMe to nicotinamide. Variants of this gene are linked to an increase in homocysteine levels.

Check your genetic data for rs694539 (23andMe v4, v5; AncestryDNA):

  • TT: 4-fold increase in the risk of migraines in women [ref]
  • CT: normal migraine risk
  • CC: decreased migraine risk

MTHFR gene: Several studies have linked the MTHFR C677T variant to an increased risk of migraines, but not all of the studies agree. This one may be a mild increase in risk or perhaps for just certain population groups.[ref]

Check your genetic data for rs1801133 (23andMe v4, v5; AncestryDNA):

  • G/G: normal risk of migraine
  • A/G: possibly increased risk of migraines
  • A/A: possibly increased risk of migraine [ref][ref][ref]

Serotonin Pathway Genes Associated with Migraines:

C7orf10 gene: codes for an enzyme involved in the production of glutarate from tryptophan (precursor for serotonin) and lysine.

Check your genetic data for rs4379368 (23andMe v4, v5; AncestryDNA):

  • C/C: normal risk of migraines
  • C/T: decreased risk of migraines
  • T/T: decreased risk of migraines (Caucasian ancestry) [ref]  (opposite found in a Chinese population)[ref]

SLC6A4 gene: codes for a serotonin transporter.

Check your genetic data for rs2066713 (23andMe v4,v5; AncestryDNA):

  • G/G: normal risk of migraines
  • A/G: decreased risk of migraines
  • A/A: decreased risk of migraines[ref]

Note that there are a lot of other genetic variants in the serotonin transport and receptor genes that have been studied and found not to be involved in migraine risk. 

Histamine / Mast Cell Activation Pathway Genes Associated with Migraines:

AOC1 gene: codes for diamine oxidase, which breaks down histamine in the gut.

Check your genetic data for rs1049793 (23andme v4; AncestryDNA):

  • C/C: normal
  • C/G: increased risk of migraines
  • G/G: increased risk of migraines [ref] (reduced DAO which breaks down histamine)
Check your genetic data for rs10156191 (23andMe v4; AncestryDNA):

  • C/C: normal
  • C/T: increased risk of migraines, especially in women
  • T/T: increased risk of migraines, especially in women [ref] (reduced DAO which breaks down histamine)

Inflammatory Pathway Genes Associated with Migraines:

TNF gene: tumor necrosis factor alpha is one of the body’s main proinflammatory cytokines.

Check your genetic data for rs3093664 (23andMe v5; AncestryDNA):

  • G/G: increased risk of menstrual migraines [ref] (increased inflammatory response)
  • A/G: increased risk of menstrual migraines
  • A/A: normal
Check your genetic data for rs1800750 (23andMe v4, v5; AncestryDNA):

  • G/G: normal risk of migraines
  • A/G: increased risk of migraines
  • A/A: increased risk of migraines [ref] (increased inflammatory response)
Check your genetic data for rs1800629 (23andMe v4, v5; AncestryDNA):

  • A/A: increased risk of migraines [ref] (increased inflammatory response)
  • A/G: increased risk of migraines
  • G/G: normal

IL1A gene: codes for interleukin-1 a which is part of the body’s inflammatory response

Check your genetic data for rs17561 (23andMe v4; AncestryDNA):

  • C/C: normal
  • A/C: increased risk of migraines
  • A/A: increased risk of migraines [ref] (increased inflammatory response)

Cholesterol Pathway Genes Associated with Migraines:

LRP1 gene:  codes for an LDL cholesterol receptor.  Migraine intensity and frequency have been linked (in a small study) to cholesterol levels.[ref]

Check your genetic data for rs11172113 (23andMe v4, v5; AncestryDNA):

  • C/C: slightly decreased risk for migraines [ref]
  • C/T: slightly decreased risk for migraines
  • T/T: normal risk for migraines

Lifehacks:

Below are some research-based options for either reducing the frequency or taking away the pain of migraines.

Tryptophan to increase serotonin, melatonin:

Serotonin is derived from the amino acid tryptophan. A study using a tryptophan-depletion diet showed that it worsened headaches and nausea in migraine sufferers.  [ref]

Tryptophan is generally abundant in diets that contain enough protein. However, if you don’t eat a lot of protein, you may want to track the amount of tryptophan you eat and increase your intake of tryptophan-containing foods such as salmon, eggs, poultry, cheese, and spinach.[ref]

Alternatively, tryptophan is available as a powdered supplement. For it to cross the blood-brain barrier, tryptophan must be eaten with carbs and without other branch chain amino acids.

Melatonin supplements:

A couple of clinical trials have evaluated the efficacy of melatonin for preventing migraines.  One study compared 3 mg melatonin to placebo and to amitriptyline (25 mg). Melatonin was shown to be significantly better than placebo, but about the same as amitriptyline. Another clinical trial compared melatonin to placebo and to sodium valproate (prescription migraine med). Melatonin again was found to be superior to placebo and similar to sodium valproate in reducing migraines. It was also found to have fewer side effects than sodium valproate. [ref][ref]

Tryptophan also is the precursor amino acid for melatonin, so supplementing with tryptophan (with carbs, without other branch chain amino acids) has been shown in studies to increase melatonin levels.

Blocking blue light (from TV, laptop, phone, bright overhead lights) at night also naturally increases your melatonin levels.

Riboflavin:

A placebo-controlled study investigated riboflavin for migraine prevention. The trial used 400 mg of riboflavin daily for 3 months. About 60% of the participants had reduced migraine frequency using riboflavin (compared to 15% placebo effect).[ref]

Riboflavin is also effective for lowering homocysteine and is important in the methylation cycle. So this may be a good ‘hack’ to try if you have either of the methylation cycle pathway variants listed above.

Aspirin:

A study that looked back over medical records for a decade found that people taking aspirin regularly as a way to prevent migraines had fewer migraines.[ref] A meta-analysis of 8 different migraine prevention studies showed that aspirin statistically reduced migraine frequency at a dose of 325mg/day (a single regular strength aspirin).[ref]  Of course, you would need to weigh the slight risk of increased bleeding with daily aspirin and talk with your doctor if you have questions on this.

Magnesium to prevent migraines:

The studies showing that people with migraines have lower magnesium levels combines well with a trial of magnesium for the prevention of migraines.  So if you think you are low in magnesium, it may be a good supplement to try. [ref] [ref]

Foods high in magnesium include legumes, nuts, chocolate, and avocados.  When it comes to supplemental magnesium, most of the migraine studies used magnesium oxide (available on Amazon). You may find that other forms of magnesium, such as magnesium glycinate are better absorbed.

Ketogenic diet for migraines?

A ketogenic diet works for certain types of epilepsy, so it makes sense that it may help with migraines as well.  And it might help, a little, maybe, for some people…  or perhaps just cleaning up your diet, in general, would help.

A study of 96 overweight women with frequent migraines investigated whether a keto diet would help. Half of the women went on a keto diet for 6 months, and the other half went on a standard lower calorie diet. Both groups met with a nutritionist to plan out their diets. The women on the keto diet went from a baseline migraine frequency of 2.9 migraines per month to 2.2 migraines per month at month 6.  The women on the standard diet went from 3.2 migraines/month to 2.4 migraines per month. [ref] You should go read the title and abstract of the study – there is a definite bias towards keto, and the results are made to sound like the keto diet worked great. But when you read through the results in the behind-a-paywall study, the standard diet group had just as much improvement over the course of the six months as the keto diet group. Perhaps a better conclusion is that meeting with a dietician helps to decrease migraine frequency a little bit.

Decreasing TNF-Alpha:

If your genetic risk factors for migraines include the TNF-alpha variants, you may want to try decreasing TNF-alpha through some natural supplements.

Black seed oil – Nigella sativa – has been shown to reduce TNF-alpha. It has also been shown in an animal study to reduce mast cell degranulation in the meninges. [ref][ref]  You can get black seed oil at your local health food store or through Amazon.

Curcumin has been shown to reduce inflammatory cytokines in the brain, including TNF-alpha. A clinical trial found that the combo of curcumin and CoQ10 was effective for reducing the number of migraines.[ref][ref] You can get curcumin in your diet by using the spice turmeric. Or it is available as a supplement on Amazon or at your local store- best absorbed with piperine included.

Circadian Rhythm and Migraines:

A study of over 2000 people with migraines found that early morning onset was quite frequent (40%). The study also found that people with chronic migraines were more tired after circadian disruption (staying up late) and less able to cope with being active during times when they weren’t normally active. [ref]

The early morning onset could be due to increased histamine levels in the early morning hours (causing mast cell degranulation) or due to increased TNF-alpha at night. [ref][ref]

Blocking blue light at night, which causes an increase in melatonin, and sticking to a routine sleep schedule may help with migraine pain.

Exercise and Migraines:

While exercise is a known trigger for some people for migraines, it also raises BDNF levels. A study of exercise and migraines suggests that regular activity may help decrease the frequency of migraines in the long run. [ref]

Heat, Cold, and Peppermint:

The TRPM8 cold/menthol receptor is active in the meningeal inflammation of a migraine. Studies show that cooling the head (ice pack) or peppermint oil (menthol) on the forehead is effective for migraine relief for some people. [ref]

Yoga:

A clinical trial of yoga found that it did reduce the frequency and intensity of migraines. [ref]

Meditation for Migraines:

A study of mindfulness meditation did not find that it statistically reduced migraines, although there was a trend towards fewer migraines/ month. [ref]

Trigger Point Therapy:

Myofascial trigger points are associated with the pain of migraines. These trigger points are often found in the areas around the trigeminal nerve.  Here is a good resource on the topic: Temporalis Trigger Points. Or if you like books: Trigger Point Therapy for Headaches and Migraines.

 

Snips about SNPs: Lactose Intolerance Gene

The LCT gene controls whether you produce lactase (enzyme that breaks down lactose) as an adult. The genetic variant that allows people to still drink milk as an adult is found in about 90% of Caucasians.  But Caucasians are the exception here, and most other populations don’t carry the variant that produces lactase as an adult.

Check your genetic data for rs4988235 (23andMe v.4, v.5; AncestryDNA):

  • A/A: Still produces lactase as an adult
  • A/G: Still produces lactase as an adult, but less than those with A/A [ref]
  • G/G: No longer produces lactase as an adult

Not a lactase producer but still wanting to eat some ice cream? Probiotics that contain lactobacillus species can usually help you to digest some milk.  [ref][ref]

Want more details? Check out the full article on Lactose Intolerance Genes

 

*SNP stands for Single Nucleotide Polymorphism, which is when one of the nucleotide bases (the A, C, G, or Ts) is replaced by a different nucleotide base in a gene.  

Snips about SNPs: ACTN3 (muscle type gene)

The ACTN3 gene codes for a type of muscle fiber found in fast-twitch skeletal muscles. These are the muscle fibers that produce explosive, powerful contractions. Think Olympic sprinters and powerlifters…

About 25% of Caucasians have a non-functioning ACTN3 genetic variant. If you carry this variant, it doesn’t mean that you can’t lift weights or run, but you may be at a slight disadvantage if you are an elite power athlete.  In fact, most Olympic sprinters and powerlifters carry the functional ACTN3 variant, Marathon and long-distance runners are more likely to carry the non-functioning version. [ref][ref]

Check your genetic data for rs1815739 (23andMe v4, v5; AncestryDNA):

  • C/C: functioning ACTN3 gene, optimal for elite power athletes
  • C/T: functioning ACTN3 gene, optimal for elite power athletes
  • T/T: non-functioning ACTN3 gene, more likely to be an endurance athlete than power athlete (in elite athletes)

Want to know more details? Read the full article on the ACTN3 gene function.

*SNP stands for Single Nucleotide Polymorphism, which is when one of the nucleotide bases (the A, C, G, or Ts) is replaced by a different nucleotide base in a gene.  

How to use your genetic data for biohacking

Biohacking is a term that is usually applied to optimizing health by utilizing tools such as supplements, peptides, biofeedback, photobiomodulation, transcranial magnetic stimulation… and more!

One more tool to add to that biohacking toolbox is utilizing your genetic data. You can easily use your genes to determine which biohacks are more likely to be effective for you.

Sequencing your genes for biohacking:

You have many options these days for getting your hands on your genetic data.  The two most common ones are through 23andMe or AncestryDNA, which cost around $99 (or less if on sale).  Both will give you some insight into your health and how to optimize yourself.  23andMe is a little easier to use since they have a nice interface for looking at your data on their website, but AncestryDNA does offer a way to download your raw DNA file and you can search the text file.  Or you could catch them both on sale (Father’s day, Mother’s day, Black Friday…) and then combine the 23andMe and AncestryDNA data together for a bigger picture.

If you want to go beyond the portion of your genome that you get from 23andMe or Ancestry, there are several options for sequencing your full genome.  Dante Labs offers a full genome sequencing from $699, which is cheap compared to what a full genome sequencing cost just a few years ago. Keep in mind that working with the data file for your full genome may involve installing specialized software to work with the file, but there are open source options available for that.

Once you have your genetic data, what can you do with it?

Your genes code for the proteins that make up your body’s tissue and systems. Different genes code for the enzymes that metabolize all of the substances you take into your body. So the great biohacking supplements that work so well for one person may not do anything for you – depending on your genes.

You can use that genetic data to find out which supplements, vitamins, or nootropics might work best for you.

Take modafinil, as an example…

Some people swear by modafinil as a nootropic, claiming it will make you more alert and mentally able to leap tall buildings. For others, modafinil may be a ‘meh’ without much of an effect.  Studies show that the effects of modafinil are based around which version of the COMT gene you carry.  (Got your genetic data? Check to see if modafinil is likely to work for you.)

Biohacking your neurotransmitters:

A lot of the nootropics and biohacking supplements on the market help people become mentally more with it — getting rid of brain fog, alleviating anxiety, lifting mood…  But before you reach for a bottle of research chemicals, try optimizing your neurotransmitters naturally first.

The methylation cycle does a lot in your body, and one function is balancing, cycling, and producing neurotransmitters.  The MTHFR enzyme is at a key point in the methylation cycle; knowing if you have genetic variants that impact MTHFR can help you to optimize your methylation cycle.  Some people with MTHFR variants optimize the pathway by adding more folate to their diet (dark leafy greens, liver, legumes) and others may use a low dose methylfolate supplement.

Another way around MTHFR variants is to make sure you get enough choline, especially if you carry genetic variants that impact choline. And a final piece to this puzzle is your COMT gene variants, which can help you to determine whether adding a bunch of methyl group supplements is a good idea — or something that may make you irritable and anxious.

Serotonin is a neurotransmitter that gets a lot of press when it comes to depression.  And serotonin is methylated to become melatonin, so it also plays a role in sleep and circadian rhythm.  Your genetic variants impact how well your body uses tryptophan to make serotonin (and melatonin). Knowing if this is a weak link for you can help to guide you on dietary hacks for increasing serotonin.

Biohacking your sleep:

There are many reasons for having problems with sleep, and you can use your genetic data to get some insight as to where to start with biohacking your sleep.

Sleep problems could be due to stress, high cortisol, and HPA axis dysfunction. Or it could have nothing to do with cortisol and chasing that pathway may be a waste of time for you. Perhaps your genetic data can help you figure that out…

Sleep issues can also be due to not producing melatonin in the right amount and at the right time.  This could be environmental (blocking blue light at night), a problem converting tryptophan, or a problem with melatonin receptors.

Insomnia can also have a variety of genetic causes. It can cause you to wake up at 4 am… or insomnia can involve not being able to fall asleep.

Biohacking your diet

I’ll be honest and say that I don’t think there is a genetically perfect diet or need for a special diet based on your genes. Instead, there are certain genetic variants that can tell you a few things to avoid or point to a couple of things to include. Optimize!  But still, allow for a lot of variety. We didn’t evolve to this level without being resilient beings.

One popular diet biohack is MCT oil and butter in your coffee instead of eating breakfast. This is probably fine for most people, but anyone with a medium-chain acyl co-a dehydrogenase deficiency mutation may struggle with this.

Going keto? Great. Unless you have either the medium or short-chain acyl co-A dehydrogenase deficiency mutation (or another inborn error of metabolism). Even carrying one copy of these mutations can cause you to feel pretty bad when trying to constantly rely on fat for fuel. These are somewhat rare diseases to have. But with multiple ‘rare’ mutations and only needing one copy of the gene to feel bad with keto, this affects a bigger percentage of the population than you would think. If you feel awful on keto, genetics may be why.

If you are going to biohack your diet by going carnivore, it is a good idea to know how you react to high amounts of saturated fats before you start scarfing down ribeyes for breakfast, lunch, and dinner.  Some people may be at a higher risk of heart disease or Alzheimer’s and need to keep a close eye on their biomarkers.

Biohacking Weight Loss:

Your genes are intricately involved in your weight. Yes, that bag of Doritos that you just ate may be the cause of your weight gain, but the driving force behind seeking out and devouring the whole bag may be in your genes.

Two of the more important genetic factors in how much you weigh are the FTO and MC4R genes. You may notice that there aren’t a lot of high-quality lifehacks listed for those genes… that is the million dollar weight loss drug that still needs to be patented.

Leptin and ghrelin are integral to your appetite and drive to eat.  Understanding your genetic propensity there may give you ideas on where to focus.

What is the most important biohacking secret?

OK, I don’t know that this is a secret at all :-)  But from all the research that I’ve read, experiments I’ve done, and genetic data that I’ve looked at the biggest bang for your buck should be ….  drumroll, please …. to optimize your circadian rhythm.

What does circadian rhythm control? Pretty much everything. Studies link circadian rhythm dysfunction to increased obesity, heart disease, various chronic diseases, Alzheimer’s, depression, bipolar disorder, Parkinson’s, and more.

Your core circadian clock is governed by the transcription and translation of some key circadian genes. And this, in turn, governs the rest of the rhythms of your body — from body temperature to cortisol fluctuation to the enzymes produced in your liver for breaking down your various biohacking supplements.

Want to read more about how your genetic variants interact with your circadian rhythm? I have a whole section on circadian genes.

Get started today…

If you have your genetic data, there is no reason not to dig into the science and figure out how to use the research for yourself.  You don’t have to pay a bunch of money for reports on your data, instead, start off by reading through the free articles on this website.  When you’ve exhausted this resource, head over to snpedia.com or pubmed.gov and start digging through the genetics research on all of the topics you are interested in.