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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.

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 (?(15)N) 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.

SUBMITTER: Lemas DJ

PROVIDER: S-EPMC3755132 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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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 DJ Klimentidis Yann C YC Wiener Howard H HH O'Brien Diane M DM Hopkins Scarlett E SE Allison David B DB Fernandez Jose R JR Tiwari Hemant K HK Boyer Bert B BB

Genes & nutrition 20130323 5

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 ...[more]

PMID: 23526194

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Project description:BackgroundAlaska Native people currently have a higher prevalence of hypertension than do nonnative Alaskans, although in the 1950s hypertension was rare among Alaska Native people. A novel biomarker of marine foods, the nitrogen isotope ratio (?¹?N) in RBCs was shown to be negatively associated with systolic and diastolic blood pressure. Few studies have examined how individual characteristics modify the association of marine food intake with blood pressure.ObjectiveThis exploratory analysis examined whether sex, adiposity, and hypertension modify the inverse association between marine food intake and blood pressure.MethodsWe used covariate-adjusted linear models to describe the association between ?¹?N and blood pressure in 873 adult Alaska Native (Yup'ik) people who resided in 8 communities in southwest Alaska. We separately stratified by sex, body mass index (BMI) group, abdominal obesity, and hypertension status and assessed the interaction between ?¹?N and participant characteristics on blood pressure via likelihood ratio tests.ResultsThe association between ?¹?N and systolic blood pressure was modified by sex, BMI status, and abdominal obesity, with the inverse association observed only in the male (? = -1.5; 95% CI: -2.4, -0.6 : , nonobese BMI (? = -1.7; 95% CI: -2.5, -1.0), and non-abdominally obese (? = -1.6; 95% CI: -2.4, -0.9) strata (all P-interaction < 0.0001). A reduction in diastolic blood pressure associated with ?¹?N was observed in the nonobese BMI (? = -1.1; 95% CI: -1.7, -0.5) and non-abdominally obese (? = -1.1; 95% CI: -1.7, -0.5) strata, although only the interaction between BMI group and ?¹?N with diastolic blood pressure was significant. The inverse association between ?¹?N and both systolic and diastolic blood pressure was observed in nonhypertensive individuals, although the comparison had limited power. The results were consistent with those identified by using combined RBC concentrations of eicosapentaenoic acid and docosahexaenoic acid as the biomarker of marine food intake, although the associations identified by using ?¹?N were larger.ConclusionsObesity status modified the inverse association between marine food intake and both systolic and diastolic blood pressure in adult Alaska Native (Yup'ik) people. The inverse association between ?¹?N and systolic blood pressure was also modified by sex.

Dataset Information

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.

Publications

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.

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