Nutritional Genomics Institute

Featured Blog: Genes and your Jeans

As our exploration and comprehension of the human genome continues to evolve, research provides us with the ability to pinpoint specific genes that may increase an individual’s propensity for certain health conditions. While revolutionary and incredibly convenient, this development comes with both good and bad news. Let’s begin with the bad, shall we?

The bad news: Your genes can negatively influence your weight.

One such gene, transmembrane protein 18 (TMEM18), has been implicated in the development of obesity and other metabolic disturbances. This gene is most often found in neurons and is copiously expressed within the hypothalamus and brain stem, both of which are key central nervous system regions in terms of feeding, reward, and gut-brain communication (Sallman Almen et al., 2010). TMEM18 may also be present in other areas of the brain that have been shown to influence food preferences and behaviors, including the amygdala, the hippocampus, and the prefrontal cortex (Rask-Anderson et al., 2012). In a rodent model, the loss of function of TMEM18 ultimately led to a greater body weight, while the over expression of this gene resulted in a decrease in energy intake and an increase in energy expenditure (Larder et al., 2017). Two TMEM18-associated single nucleotide polymorphisms (SNPs), rs6548238 and rs4854344, displayed positive correlations to both waist circumference and body weight and also carried increased risks of obesity in a population of Greek children (Rask-Anderson et al., 2012). A study conducted on Swedish children also investigated rs6548238 as well as rs756131 and found that both SNPs were strongly associated with an increased risk of obesity (Sallman Almen et al., 2010). Lastly, two additional SNPs, rs17042334 (associated with insulin abnormalities) and rs17729501 (associated with obesity), may serve as valuable biomarkers, as they appear to affect the binding and expressive abilities of TMEM18 (Wiemerslage et al., 2016). Ultimately, TMEM18 and its associated SNPs comprise just a piece of the complex puzzle that is energy balance and weight maintenance in the human body. As evidenced above, mutations or alterations in the expression of TMEM18 often have less-than-desirable effects on weight—so where is the positive in all of this?

The good news: Your lifestyle can influence the expression of your genes.

Rejoice! Your genes do not necessarily determine your destiny. 

 In fact, there are several lifestyle interventions that may be helpful in optimizing the function of the TMEM18 gene and its related SNPs.

Exercise: TMEM18 SNP rs4854344 has been strongly linked to increased BMI and body weight in Caucasians; however, when children and adolescents participated in a daily physical activity program, their waist circumference and BMI measurements significantly improved (Zlatohlavek et al., 2018). 

 In other words, the impact of the SNP did not prevent the positive effects of regular exercise from occurring. So—keep moving!

Fasting: In adult flies, TMEM18 expression was drastically reduced—by almost 80 percent—after just 12 hours of starvation; this led to decreased TMEM18 expression in the brain, which may be further implicated in metabolic imbalances and dysfunction (Wiemerslage et al., 2016). 

 Therefore, fasting for an extended period of time may negatively impact TMEM18 and overall metabolism.

Fat Intake: When rats were fed a high-fat diet (60 percent fat) for six weeks, TMEM18 was down regulated in the hypothalamus, liver, and soleus muscle as compared to chow-fed rats (Gutierrez-Aguilar, Kim, Woods, & Seeley, 2012). 

 Thus, a high-fat diet may not be the best option for an individual with alterations in TMEM18, as it may lead to both excessive caloric intake as well as a decrease in the expression of this gene.

Our genes will always play a role in our health. 

 However, the ever-changing realms of epigenetics and nutrigenomics tell us that we have the ability to take our wellbeing into our own hands

and I cannot imagine anything more empowering.


Gutierrez-Aguilar, R., Kim, D.H., Woods, S.C., & Seeley, R.J. (2012). Expression of new loci associated with obesity in diet-induced obese rats: from genetics to physiology. Obesity, 20(2), 306-312.

Larder, R., Sim, M.F.M., Gulati, P., Antrobus, R., Tung, Y.C.L., Rimmington, D.,…Coll, A.P. (2017). Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation. Proceedings of the National Academy of Sciences of the United States of America, 114(35), 9421-9426.

Rask-Anderson, M., Jacobsson, J.A., Moschonis, G., Chavan, R.A., Sikder, M.A.N., Allzen, E.,…Schioth, H.B. (2012). Association of TMEM18 variants with BMI and waist circumference in children and correlation of mRNA expression in the PFC with body weight in rats. European Journal of Human Genetics, 20(2), 192-197.

Sallman Almen, M., Jacobsson, J.A., Shaik, J.H.A., Olszewski, P.K., Cedernaes, J., Alsio, J.,…Schioth, H.B. (2010). The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children. BMC Medical Genetics, 11, 58.

Wiemerslage, L., Gohel, P.A., Maestri, G., Hilmarsson, T.G., Mickael, M., Fredriksson, R.,…Schioth, H.B. (2016). The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling. Journal of Endocrinology, 229(3), 233-243.

Zlatohlavek, L., Maratka, V., Tumova, E., Ceska, R., Lanska, V., Vrablik, M., & Hubacek, J.A. (2018). Body adiposity changes after lifestyle interventions in children/adolescents and the NYD-SP18 and TMEM18 variants. Medical Science Monitor, 24, 7493-7498.

Blog Posts

Genes, Weight Loss, & SPIT!

February, 3, 2019

Yes, you read that correctly. Your spit (aka saliva) can be a factor in determining how easy or difficult it is for you to lose weight. This is because your saliva contains an enzyme called salivary amylase which is responsible for initiating the breakdown of starch. By NGI Intern, Alex Bear

AMY1 Copy Number Variants

One of the genes which codes for amylase is called AMY1, and the AMY1 gene has a wide range of copy number variants (CNV) associated with it. Individuals can carry anywhere from 1 to 15 copies of the AMY1 gene in their genome. (1) Individuals who have high AMY1 CNV have been shown to be less likely to develop obesity and have more success in losing fat when implementing a low-calorie diet than individuals with low AMY1 CNV. (2(p1) 3) These effects are likely due to better blood glucose regulation amongst individuals with high AMY1 CNV. (3)


So, the fewer copies of AMY1 that you have, the more important it is to minimize the ingestion of starchy foods to reach your weight loss goals. This is true even if the starchy foods are of high quality such as authentic sourdough bread or heirloom potatoes. If you are fortunate enough to have 10-15 copies of AMY1, you may consider reducing your total current caloric intake while maintaining your consumption of nutrient-dense starches.

Best of luck in your weight loss goals! Please feel free to comment or contact us with any questions!

This gene is found on the New NGI DietDx Panel scheduled for release in March, 2019

1. Mandel AL, Breslin PAS. High Endogenous Salivary Amylase Activity Is Associated with Improved Glycemic Homeostasis following Starch Ingestion in Adults123. J Nutr. 2012;142(5):853-858. doi:10.3945/jn.111.156984

2. Pinho S, Padez C, Manco L. High AMY1 copy number protects against obesity in Portuguese young adults. Ann Hum Biol. September 2018:1-5. doi:10.1080/03014460.2018.1490452

3. Heianza Y, Sun D, Wang T, et al. Starch Digestion-Related Amylase Genetic Variant Affects 2-Year Changes in Adiposity in Response to Weight-Loss Diets: The POUNDS Lost Trial. Diabetes. 2017;66(9):2416-2423. doi:10.2337/db16-1482

The Fat Fad: Assessing the Ketogenic Diet and its Applications

April 9, 2019

The Fat Fad: Assessing the Ketogenic Diet and its Applications

The classic ketogenic diet is characterized by consuming a high fat, low protein, and low carbohydrate diet to mimic the fasting state and utilize fats as the primary source of fuel in the body (Meira et al., 2019). This lifestyle first gained traction in the early 1920s when similar to starvation, it displayed the ability to produce ketone bodies and reduce seizure incidence and severity in individuals with epilepsy (Meira et al., 2019). While the ketogenic diet’s effects on seizure disorders are well-documented, it is important to ask: Is this diet safe for everyone? Let’s explore.

The ketogenic diet is not without adverse effects.

Children who are placed on a long-term ketogenic diet have an increased risk of growth deficiency, kidney stones, skeletal fractures, dyslipidemia, vitamin D deficiency, acute pancreatitis, and prolonged QT intervals (Vining, 2008). In their study of children who followed the ketogenic diet from 2003 to 2012, Wibisono et al. (2015) reported that constipation, hypertriglyceridemia, and hypercholesterolemia were the most common side effects, whereas diarrhea, lethargy, iron deficiency, and vomiting occurred less frequently. Similarly, Liu et al. (2018) stated that adults adhering to this diet tended to display elevated low-density lipoprotein (LDL) and total cholesterol in addition to menstrual irregularities in female patients.

Furthermore, Asrih, Altirriba, Rohner-Jeanrenaud, and Jornayvaz (2015) found that, after just four weeks on a ketogenic diet, inflammation as well as lipid and macrophage accumulation in the liver had increased. Interestingly, the authors also found that inflammation was decreased in white adipose tissue, which suggests that the ketogenic diet may produce favorable effects in one body tissue and less-than-desirable effects in another.

Due to the restrictive nature of the ketogenic diet, it is recommended that individuals supplement with vitamin D, calcium, and B vitamins, among other micronutrients (Kossoff et al., 2018). Additionally, supplementing with potassium citrate may help to ameliorate the occurrence of kidney stones (Wibisono et al., 2015).

The ketogenic diet can impact our biochemistry and gene expression.

According to Kossoff et al. (2018), it is of the utmost importance to screen a child for disorders of fatty acid transport before beginning a ketogenic diet. These include several inborn errors that can be found in organic acids testing, porphyrin testing, and in genomic evaluations:

Carnitine deficiency (primary)

Carnitine palmitoyltransferase (CPT) I or II deficiency

Carnitine translocase deficiency

ß-oxidation defects

Medium-chain acyl dehydrogenase deficiency (MCAD)

Long-chain acyl dehydrogenase deficiency (LCAD)

Short-chain acyl dehydrogenase deficiency (SCAD)

Long-chain 3-hyroxyacyl-CoA deficiency

Medium-chain 3-hydroxyacyl-CoA deficiency

Pyruvate carboxylase deficiency


Often times, many of our modern idiopathic diseases are heterozygous or partial presentations of some of our more well-known metabolic disturbances. Unfortunately, due to their heterogenous presentation, they often go misdiagnosed for many years, leaving parents confused and individuals at risk for long term consequences.

In addition to these inborn errors, the FTO, APOE, and PPAR genes also influence fat metabolism, so it is vital that SNPs in these genes are assessed before prescribing the ketogenic diet. Variations in APOE genotypes may explain differences in fat metabolism, as carriers of E4 tend to experience more significant lowering of total cholesterol and apolipoprotein B levels when dietary saturated fat is replaced with low-glycemic carbohydrates (Griffin et al., 2018). Furthermore, Asrih et al. (2015) found that the ketogenic diet downregulated FGFR4 and KLB and impaired FGF21 signaling in the liver, all of which may play a role in the onset and progression of liver inflammation and altered lipid metabolism.

In addition to impacts on mitochondrial function and lipid metabolism, the ketogenic diet has been shown to increase adenosine and diminish or even block methylation (Boison, 2017). Thus, those with detoxification deficiencies or genomic impairments in methylation should likely avoid this diet unless otherwise supported.

Ultimately, caution must be exercised when prescribing or following the ketogenic diet, especially for the long term. It is highly recommended that functional testing is performed prior to placing an individual on this diet, and, at the very least, he or she should be screened regularly for any adverse effects.

Diet is never a one-size-fits-all approach, 

and the ketogenic diet is no exception to that rule.


Asrih, M., Altirriba, J., Rohner-Jeanrenaud, F., & Jornayvaz, F.R. (2015). Ketogenic diet impairs FGF21 signaling and promotes differential inflammatory responses in the liver and white adipose tissue. PLoS One, 10(5), e0126364.

Boison, D. (2017). New insights into the mechanisms of the ketogenic diet. Current Opinion in Neurology, 30(2), 187-192.

Griffin, B.A., Walker, C.G., Jebb, S.A., Moore, C., Frost, G.S., Goff, L.,…Lovegrove, J.A. (2018). APOE4 genotype exerts greater benefit in lowering plasma cholesterol and apolipoprotein B than wild type (E3/E3), after replacement of dietary saturated fats with low glycaemic index carbohydrates. Nutrients, 10(10), 1524.

Kossoff, E.H., Zupec-Kania, B.A., Auvin, S., Ballaban-Gil, K.R., Christina Bergqvist, A.G., Blackford, R.,…Wirrell, E.C. (2018). Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open, 3(2), 175-192.

Liu, H., Yang, Y., Wang, Y., Tang, H., Zhang, F., Zhang, Y.,…Zhao, Y. (2018). Ketogenic diet for treatment of intractable epilepsy in adults: a meta-analysis of observational studies. Epilepsia Open, 3(1), 9-17.

Meira, I.D., Romao, T.T., Pires do Prado, H.J., Kruger, L.T., Paiva Pires, M.E., & da Conceicao, P.O. (2019). Ketogenic diet and epilepsy: what we know so far. Frontiers in Neuroscience, 13, 5.

Vining, E.P.G. (2008). Long-term health consequences of epilepsy diet treatments. Epilepsia, 49(s8), 27-29. Wibisono, W., Rowe, N., Beavis, E., Kepreotes, H., Mackie, F.E., Lawson, J.A.,…Cardamone, M. (2015). Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance. The Journal of Pediatrics, 166(4), 1030-1036.

The Genetics of Love and Commitment 

February 10, 2019

Although Forest Gump is a fictional character, I’ve always admired what he represents: unwavering, passionate commitment. 

Men like Forest and others like Hugh Jackman (married since 1996!) have set quite a standard for the rest of us! As it turns out, real men who share these traits of remarkable commitment and compassion do actually exist, and, as you may have guessed, carry similar genetic profiles.

What are these commitment genes and how does he provide the sample before the first date?!?-----women everywhere

A study in male voles showed that the vasopressin receptor 1a gene (AVPR1A) predicted monogamous behavior and that in humans (thankfully, all men are not voles), variants of this gene were correlated with the quality of marital relationships.1 

This means that men without variations in this gene have better marriages? 

What else do we know? 

We know that women married to men with alterations in this gene, the AVPR1A RS3 polymorphism, even display less affection towards their partners.1 However, there are always two sides to every story! We also know that women who carry alterations in this gene are known to have pair-bonding outside of their marriages…aka more extra marital affairs. Thus, it appears that for either sex, having a genetic alteration in this gene could potentially influence your probability of divorce over long term marriage success. 

This one gene can't be the end all be all of relationship success, right?

Oxytocin is often called the "love hormone"...It is released when you cuddle and when you orgasm! This one must be important!

Another study showed a correlation between variation in the oxytocin receptor (OXTR) gene and "prosocial" behavior (aka the intention to benefit others).2 Those who had two G alleles of the rs53576 SNP in OXTR tended to be more prosocial than those who carried the A allele. Specifically, when their partner was describing a time of great suffering in their lives (the Starbucks line was so long today honey!), the GG individuals maintained open body posture, eye contact, and smiled for longer than GA or AA individuals. This gene (and many others) relates to how attentive one may be in a relationship and therefore may influence long term pair-bonding behavior.

Of course, regardless of genetics, we all have the ability to commit and to show great compassion towards our partners; but for some folks, these qualities may come more naturally than for others! 

We hope that Valentine's Day dinners everywhere are enjoyable and do not require a prerequisite gene test...but if you are falling in love and want to know, you know where to find us! Peace, Love and Genomics!~NGI


1. Walum H, Westberg L, Henningsson S, et al. Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. Proc Natl Acad Sci U S A. 2008;105(37):14153-14156. doi:10.1073/pnas.0803081105

2. Kogan A, Saslow LR, Impett EA, Oveis C, Keltner D, Rodrigues Saturn S. Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition. Proc Natl Acad Sci U S A. 2011;108(48):19189-19192. doi:10.1073/pnas.1112658108

Photo source:

Written by: Alex Bear and NGI