title: 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 (δ(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.
authors.affiliation: Institute of Arctic Biology, Center for Alaska Native Health Research, University of Alaska Fairbanks, 311 Irving I Building, PO Box 757000, Fairbanks, AK, 99775-7000, USA, dominck.lemas@ucdenver.edu.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Lemas
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.forename: Howard H
authors.initials: HH
authors.lastname: Wiener
authors.forename: Diane M
authors.initials: DM
authors.lastname: O'Brien
authors.forename: Scarlett E
authors.initials: SE
authors.lastname: Hopkins
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Jose R
authors.initials: JR
authors.lastname: Fernandez
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
authors.forename: Bert B
authors.initials: BB
authors.lastname: Boyer