Smith CE; Follis JL; Dashti HS; Tanaka T; Graff M; Fretts AM; et al. - - Mol Nutr Food Res 2017; in press.
SCOPE: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.
METHODS AND RESULTS: We conducted a genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis. Data from 9 discovery studies (up to 25,513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (P-interaction <10-7) , and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17,675 individuals. Variant rs9635058 (128 kb 3′ of LINC00333) was replicated (P-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (P-interaction = 7.36 x 10-8) such that each serving of low-fat dairy was associated with 0.225 kg/m2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure.
CONCLUSIONS: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.