Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup'ik people

Dominick J. Lemas, Yann C. Klimentidis, Howard H. Wiener, Diane M. O'Brien, Scarlett E. Hopkins, David B. Allison, Jose R. Fernandez, Hemant K. Tiwari, Bert Boyer

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

n-3 Polyunsaturated fatty acids (n-3 PUFAs) have anti-obesity effects that may modulate risk of obesity, in part, through interactions with genetic factors. Genome-wide association studies (GWAS) have identified genetic variants associated with body mass index (BMI); however, the extent to which these variants influence adiposity through interactions with n-3 PUFAs remains unknown. We evaluated 10 highly replicated obesity GWAS single nucleotide polymorphisms (SNPs) for individual and cumulative associations with adiposity phenotypes in a cross-sectional sample of Yup'ik people (n = 1,073) and evaluated whether genetic associations with obesity were modulated by n-3 PUFA intake. A genetic risk score (GRS) was calculated by adding the BMI-increasing alleles across all 10 SNPs. Dietary intake of n-3 PUFAs was estimated using nitrogen stable isotope ratio (δ15N) of red blood cells, and genotype-phenotype analyses were tested in linear models accounting for familial correlations. GRS was positively associated with BMI (p = 0.012), PBF (p = 0.022), ThC (p = 0.025), and waist circumference (p = 0.038). The variance in adiposity phenotypes explained by the GRS included BMI (0.7 %), PBF (0.3 %), ThC (0.7 %), and WC (0.5 %). GRS interactions with n-3 PUFAs modified the association with adiposity and accounted for more than twice the phenotypic variation (~1-2 %), relative to GRS associations alone. Obesity GWAS SNPs contribute to adiposity in this study population of Yup'ik people and interactions with n-3 PUFA intake potentiated the risk of fat accumulation among individuals with high obesity GRS. These data suggest the anti-obesity effects of n-3 PUFAs among Yup'ik people may, in part, be dependent upon an individual's genetic predisposition to obesity.

Original languageEnglish (US)
Pages (from-to)495-505
Number of pages11
JournalGenes and Nutrition
Volume8
Issue number5
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Adiposity
Omega-3 Fatty Acids
Obesity
Phenotype
Body Mass Index
Single Nucleotide Polymorphism
Nitrogen Isotopes
Waist Circumference
Genetic Predisposition to Disease
Linear Models
Erythrocytes
Fats
Alleles
Genotype
Population

Keywords

  • δN
  • Adiposity
  • Alaska Native
  • BMI
  • CANHR
  • ETV5
  • FTO
  • Gene-by-environment interactions
  • Genetic risk score
  • rs7647305
  • rs9939609
  • SNP

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Genetics

Cite this

Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup'ik people. / Lemas, Dominick J.; Klimentidis, Yann C.; Wiener, Howard H.; O'Brien, Diane M.; Hopkins, Scarlett E.; Allison, David B.; Fernandez, Jose R.; Tiwari, Hemant K.; Boyer, Bert.

In: Genes and Nutrition, Vol. 8, No. 5, 01.09.2013, p. 495-505.

Research output: Contribution to journalArticle

Lemas, Dominick J. ; Klimentidis, Yann C. ; Wiener, Howard H. ; O'Brien, Diane M. ; Hopkins, Scarlett E. ; Allison, David B. ; Fernandez, Jose R. ; Tiwari, Hemant K. ; Boyer, Bert. / Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup'ik people. In: Genes and Nutrition. 2013 ; Vol. 8, No. 5. pp. 495-505.
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abstract = "n-3 Polyunsaturated fatty acids (n-3 PUFAs) have anti-obesity effects that may modulate risk of obesity, in part, through interactions with genetic factors. Genome-wide association studies (GWAS) have identified genetic variants associated with body mass index (BMI); however, the extent to which these variants influence adiposity through interactions with n-3 PUFAs remains unknown. We evaluated 10 highly replicated obesity GWAS single nucleotide polymorphisms (SNPs) for individual and cumulative associations with adiposity phenotypes in a cross-sectional sample of Yup'ik people (n = 1,073) and evaluated whether genetic associations with obesity were modulated by n-3 PUFA intake. A genetic risk score (GRS) was calculated by adding the BMI-increasing alleles across all 10 SNPs. Dietary intake of n-3 PUFAs was estimated using nitrogen stable isotope ratio (δ15N) of red blood cells, and genotype-phenotype analyses were tested in linear models accounting for familial correlations. GRS was positively associated with BMI (p = 0.012), PBF (p = 0.022), ThC (p = 0.025), and waist circumference (p = 0.038). The variance in adiposity phenotypes explained by the GRS included BMI (0.7 {\%}), PBF (0.3 {\%}), ThC (0.7 {\%}), and WC (0.5 {\%}). GRS interactions with n-3 PUFAs modified the association with adiposity and accounted for more than twice the phenotypic variation (~1-2 {\%}), relative to GRS associations alone. Obesity GWAS SNPs contribute to adiposity in this study population of Yup'ik people and interactions with n-3 PUFA intake potentiated the risk of fat accumulation among individuals with high obesity GRS. These data suggest the anti-obesity effects of n-3 PUFAs among Yup'ik people may, in part, be dependent upon an individual's genetic predisposition to obesity.",
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