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Nat Genet. 2017 Aug;49(8):1174-1181. doi: 10.1038/ng.3912. Epub 2017 Jul 10.

Genotype-covariate interaction effects and the heritability of adult body mass index.

Author information

1
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
2
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
3
Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
4
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
5
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
6
Estonian Genome Center, University of Tartu, Tartu, Estonia.
7
Division of Endocrinology, Boston Children's Hospital, Cambridge, Massachusetts, USA.
8
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
9
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
10
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
11
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
12
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
13
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
14
Stockholm School of Economics, Stockholm, Sweden.
15
Center for Experimental Social Science, Department of Economics, New York University, New York, New York, USA.

Abstract

Obesity is a worldwide epidemic, with major health and economic costs. Here we estimate heritability for body mass index (BMI) in 172,000 sibling pairs and 150,832 unrelated individuals and explore the contribution of genotype-covariate interaction effects at common SNP loci. We find evidence for genotype-age interaction (likelihood ratio test (LRT) = 73.58, degrees of freedom (df) = 1, P = 4.83 × 10-18), which contributed 8.1% (1.4% s.e.) to BMI variation. Across eight self-reported lifestyle factors, including diet and exercise, we find genotype-environment interaction only for smoking behavior (LRT = 19.70, P = 5.03 × 10-5 and LRT = 30.80, P = 1.42 × 10-8), which contributed 4.0% (0.8% s.e.) to BMI variation. Bayesian association analysis suggests that BMI is highly polygenic, with 75% of the SNP heritability attributable to loci that each explain <0.01% of the phenotypic variance. Our findings imply that substantially larger sample sizes across ages and lifestyles are required to understand the full genetic architecture of BMI.

PMID:
28692066
DOI:
10.1038/ng.3912
[Indexed for MEDLINE]

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