DNA and Obesity/Diabetes

Am I Fat Because of My DNA?

There are a small number of people who may be fat due to faulty genetics (Lorenzo DN, Bennett V. Cell-autonomous adiposity through increased cell surface GLUT4 due to ankyrin-B deficiency. Proc Natl Acad Sci U S A. 2017;114(48):12743-12748.).

If not much of the fault can likely be blamed on your genes, but just how much can be? From (Sandholt CH, Vestmar MA, Bille DS, Borglykke A, Almind K, Hansen L, Sandbæk A, Lauritzen T, Witte D, Jørgensen T, Pedersen O, Hansen T. Studies of metabolic phenotypic correlates of 15 obesity associated gene variants. PLoS One. 2011;6(9)).

Five of the 15 gene variants associated with overweight, obesity and/or morbid obesity. Per allele ORs ranged from 1.15-1.20 for overweight, 1.10-1.25 for obesity, and 1.41-1.46 for morbid obesity. Five of the 15 variants moreover associated with increased measures of adiposity.

BDNF rs4923461 displayed a borderline BMI-dependent protective effect on type 2 diabetes (0.87 (0.78-0.96, p = 0.008)), whereas SH2B1 rs7498665 associated with nominally BMI-independent increased risk of type 2 diabetes (1.16 (1.07-1.27, p = 7.8×10(-4))).

Another study on obesity and genetics (Gudmar Thorleifsson, G Bragi Walters[…]Kari Stefansso. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nature Genetics volume 41, pages 18–24 (2009)).

Here’s another study on obesity and genetics (Sungshim Lani Park, Iona Cheng, Sarah A. Pendergrass, Anna M. Kucharska-Newton, Unhee Lim, Jose Luis Ambite, Christian P. Caberto, Kristine R. Monroe, Fredrick Schumacher, Lucia A. Hindorff, Matthew T. Oetjens, Sarah Wilson, Robert J. Goodloe, Shelly-Ann Love, Brian E. Henderson, Laurence N. Kolonel, Christopher A. Haiman, Dana C. Crawford, Kari E. North, Gerardo Heiss, Marylyn D. Ritchie, Lynne R. Wilkens, Loïc Le Marchand; Association of the FTO Obesity Risk Variant rs8050136 With Percentage of Energy Intake From Fat in Multiple Racial/Ethnic Populations: The PAGE Study, American Journal of Epidemiology, Volume 178, Issue 5, 1 September 2013, Pages 780–790).

A similar paper on genetics and Type 2 Diabetes (McCarthy MI1, Zeggini E. Genome-wide association studies in type 2 diabetes. Curr Diab Rep. 2009 Apr;9(2):164-71).

Macronutrient Sensitivity and Genetics

My own AncestryDNA data shows an inconclusive result with one less of a carb seeker, one intermediate and one more of a carb seeker:

#ChromPositionSNP IDReliabilityGenotypePhenotypePopulationReferences
1chr2161894663rs197273AA
AG
GG
More a carbohydrate seeker
Intermediate
Less a carbohydrate seeker
European
2chr1949248730rs838145GG
GA
AA
More a carbohydrate seeker
Intermediate
Less a carbohydrate seeker
European
3chr5167226979rs1549309AA
AG
GG
More a carbohydrate seeker
Intermediate
Less a carbohydrate seeker
European
4chr85764942rs2840445GG
GA
AA
More a carbohydrate seeker
Intermediate
Less a carbohydrate seeker
European
5chr1451323742rs8019546AA
AG
GG
More a carbohydrate seeker
Intermediate
Less a carbohydrate seeker
European

This data is based on this study (Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake).

Signif. log(p) Effect Size / Odds Ratio

Confidence

Interval

rs

Reported

Allele

+ Strand

Allele

Allele

Frequency

Trait Genes
9.4 0.22 (Fat)
[0.14-0.3] % decrease
rs838145 G G 0.46 FGF21 Dietary macronutrient intake
9 0.1 (Protein)
[0.061-0.139] % increase
rs1421085 C C 0.42 FTO Dietary macronutrient intake
6.52 0.23 (Carbohydrate)
[0.15-0.31] % increase
rs838145 G G 0.46 FGF21 Dietary macronutrient intake
6.15 0.22 (Carbohydrate)
[0.14-0.3] % increase
rs838147 A A 0.48 Intergenic Dietary macronutrient intake
5.7 0.27 (Carbohydrate)
[0.15-0.39] % increase
rs1549309 A A 0.17 Intergenic Dietary macronutrient intake
5.3 0.22 (Carbohydrate)
[0.12-0.32] % decrease
rs2840445 A A 0.27 Intergenic Dietary macronutrient intake
5.3 0.22 (Carbohydrate)
[0.12-0.32] % increase
rs8019546 A A 0.3 Intergenic Dietary macronutrient intake

AncestryDNA Raw Data Format

AncestryDNA Raw Data Format. From the site:

The information that you’ll receive with your AncestryDNA raw data will include the ‘rs’ ID where possible, chromosome, and the base pair position on the human reference genome (GRCh37). The genotype (the observed alleles at each position) will be provided on the forward strand. The raw DNA data provided has passed the AncestryDNA data quality filters.

An example of raw DNA data looks like:

rsIDchromosomepositionallele1allele2
rs4477212172017AA
rs30943151742429AA
rs31319721742584GG
rs121248191766409GG

It looks like from my data that ancestry.com tests about half of these genes. That’s unfortunate from a health perspective. Maybe the select other genes which are more genetically heritable?