1 Epidemiology, Biostatistics and Biodemography, Department of Public Health, Det Sundhedsvidenskabelige Fakultet, SDU2 Human Genetics, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU3 University of Cambridge4 MRC Unit for Lifelong Health and Ageing,University College London, London WC1B 5JU5 Epidemiology, Biostatistics and Biodemography, Department of Public Health, Det Sundhedsvidenskabelige Fakultet, SDU
Background: It has been shown recently that whole genome data can facilitate estimation of genetic contributions to a variety of traits via a mixed model framework as implemented in GCTA and R/SAS (Yang et al. Nat Genet 2010, 42:565-9; Zhao & Luan. J Prob Stat 2012, doi 10.1155/ 2012.485174). Our aim was to use this approach to investigate the life course variations in heritability of body size. Methods: We analysed height, weight and body mass index variables at 11 time-points in 2,452 individuals (1,225 men, 1,227 women) born in 1946 and enrolled in the MRC National Survey of Health and Development (NSHD), with genotypes at 147,949 single nucleotide polymorphisms (SNPs) on Metabochips which were subsequently imputed to 506,255 according to the 1000Genomes project. We obtained genome-wide kinship matrices using genotypes at SNPs on Metabochips and genotypes at all SNPs, which were used in mixed models as implemented in the computer program GCTA. Results were also compared to those obtained using an alternative procedure of kinship estimation in PLINK and mixed models in R. Results: In line with earlier findings that specific genetic variants have variable temporal effects in this cohort (Hardy et al. Hum Mol Genet. 2010; 19:545-552), we observed age-related variations in heritability estimates. Estimates based on genotypes at SNPS on Metabochips and genotypes at all SNPs were comparable but generally lower than recently reported GCTA estimates with mean(range) being 0.09(0-0.50), 0.11(0-0.20), 0.10(0-0.22) for height, weight and body mass index, respectively. Variation in estimates was also seen between alternative procedures. Conclusion: This work supports the utility of large-scale genotype data in heritability estimation and highlights the age-related variability in genetic contributions to body size across the life course. Further work will be to distinguish the effects of established variants and to consider estimates in a unified longitudinal model including contrast with models assuming various degrees of temporal homoscedasticity.
Main Research Area:
American Society of Human Genetics annual meeting 2013