Genomic inflation factors under polygenic inheritance

Yang, J., Weedon, M.N., Purcell, S., Lettre, G., Estrada, K., Willer, C.J., Smith, A.V., Ingelsson, E., O'Connell, J.R., Mangino, M., Magi, R., Madden, P.A., Heath, A.C., Nyholt, D.R., Martin, N.G., Montgomery, G.W., Frayling, T.M., Hirschhorn, J.N., McCarthy, M.I., Goddard, M.E., & Visscher, P.M. (2011) Genomic inflation factors under polygenic inheritance. European Journal of Human Genetics, 19(7), pp. 807-12.

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Population structure, including population stratification and cryptic relatedness, can cause spurious associations in genome-wide association studies (GWAS). Usually, the scaled median or mean test statistic for association calculated from multiple single-nucleotide-polymorphisms across the genome is used to assess such effects, and 'genomic control' can be applied subsequently to adjust test statistics at individual loci by a genomic inflation factor. Published GWAS have clearly shown that there are many loci underlying genetic variation for a wide range of complex diseases and traits, implying that a substantial proportion of the genome should show inflation of the test statistic. Here, we show by theory, simulation and analysis of data that in the absence of population structure and other technical artefacts, but in the presence of polygenic inheritance, substantial genomic inflation is expected. Its magnitude depends on sample size, heritability, linkage disequilibrium structure and the number of causal variants. Our predictions are consistent with empirical observations on height in independent samples of ~4000 and ~133,000 individuals.

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ID Code: 91910
Item Type: Journal Article
Refereed: Yes
Keywords: Adolescent, Adult, Computer Simulation, Genome/*genetics, Genome-Wide Association Study, Humans, Models, Genetic, Multifactorial Inheritance/*genetics, Polymorphism, Single Nucleotide, Quantitative Trait Loci/genetics, Young Adult
DOI: 10.1038/ejhg.2011.39
ISSN: 1476-5438
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 17 Jan 2016 23:23
Last Modified: 20 Jan 2016 03:56

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