Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Mol Nutr Food Res. 2018 Feb;62(3):10.1002/mnfr.201700347. doi: 10.1002/mnfr.201700347. Epub 2017 Dec 11.

Abstract

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.

Keywords: CHARGE consortium; body mass index; dairy intake; genome-wide interaction study; meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Adult
  • Aged
  • Body Mass Index*
  • Cohort Studies
  • Cross-Sectional Studies
  • Dairy Products*
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Frequency
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Myosin-Light-Chain Phosphatase / genetics
  • Polymorphism, Single Nucleotide*

Substances

  • ACTA2 protein, human
  • Actins
  • Myosin-Light-Chain Phosphatase
  • PPP1R12A protein, human