Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent.
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: 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 was conducted. Data from nine 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 × 10-8) such that each serving of low-fat dairy was associated with 0.225 kg m-2 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. CONCLUSION: 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.
Smith, CE; Follis, JL; Dashti, HS; Tanaka, T; Graff, M; Fretts, AM; Kilpeläinen, TO; Wojczynski, MK; Richardson, K; Nalls, MA; Schulz, C-A; Liu, Y; Frazier-Wood, AC; van Eekelen, E; Wang, C; de Vries, PS; Mikkilä, V; Rohde, R; Psaty, BM; Hansen, T; Feitosa, MF; Lai, C-Q; Houston, DK; Ferruci, L; Ericson, U; Wang, Z; de Mutsert, R; Oddy, WH; de Jonge, EAL; Seppälä, I; Justice, AE; Lemaitre, RN; Sørensen, TIA; Province, MA; Parnell, LD; Garcia, ME; Bandinelli, S; Orho-Melander, M; Rich, SS; Rosendaal, FR; Pennell, CE; Kiefte-de Jong, JC; Kähönen, M; Young, KL; Pedersen, O; Aslibekyan, S; Rotter, JI; Mook-Kanamori, DO; Zillikens, MC; Raitakari, OT; North, KE; Overvad, K; Arnett, DK; Hofman, A; Lehtimäki, T; Tjønneland, A; Uitterlinden, AG; Rivadeneira, F; Franco, OH; German, JB; Siscovick, DS; Cupples, LA; Ordovás, JM
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