| Summary: | 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 BMI; however the extent to which these variants influence adiposity through interactions with n‐3 PUFAs is unknown. We evaluated 10 obesity GWAS SNPs for associations with adiposity phenotypes in a cross‐sectional sample of Yup'ik people (n=1073) and evaluated whether genetic associations with obesity were modulated by n‐3 PUFA intake. n‐3 PUFAs intake was estimated using nitrogen stable isotope ratios (δ 15 N) of red blood cells and genotype‐phenotype analyses were tested in linear models accounting for familial correlations. FTO was positively associated with percent body fat and ETV5 was negatively associated with hip and thigh circumference. A genetic risk score (GRS) was positively associated with adiposity. 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. GRS 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, in part, may be dependent upon an individual's genetic predisposition to obesity.
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