Genomic inflation factors under polygenic inheritance.
paper
Cited
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- Authors
- Yang, Jian; Weedon, Michael N; Purcell, Shaun; Lettre, Guillaume; Estrada, Karol; Willer, Cristen J; Smith, Albert V; Ingelsson, Erik; O'Connell, Jeffrey R; Mangino, Massimo; MΓ€gi, Reedik; Madden, Pamela A; Heath, Andrew C; Nyholt, Dale R; Martin, Nicholas G; Montgomery, Grant W; Frayling, Timothy M; Hirschhorn, Joel N; McCarthy, Mark I; Goddard, Michael E; Visscher, Peter M; GIANT Consortium
- Year
- 2011
- Journal
- European journal of human genetics : EJHG
- PMID
- 21407268
- DOI
- 10.1038/ejhg.2011.39
- PMCID
- PMC3137506
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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| Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. | Ferreira MA et al. | β | 2014 | β |
| Genome-wide Association Study of Integrated Meat Quality-related Traits of the Duroc Pig Breed. | Lee T et al. | β | 2014 | β |
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| A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. | Wang JC et al. | β | 2013 | β |
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| Genome-wide association of body fat distribution in African ancestry populations suggests new loci. | Liu CT et al. | β | 2013 | β |
| Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. | Verhoeven VJ et al. | β | 2013 | β |
| GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. | Rietveld CA et al. | β | 2013 | β |
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| Genome-wide association meta-analysis identifies new endometriosis risk loci. | Nyholt DR et al. | β | 2012 | β |
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| Rare copy number variants in tourette syndrome disrupt genes in histaminergic pathways and overlap with autism. | Fernandez TV et al. | β | 2012 | β |
| Synthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height. | Lui JC et al. | β | 2012 | β |
| The genetic architecture of economic and political preferences. | Benjamin DJ et al. | β | 2012 | β |
| Extent of height variability explained by known height-associated genetic variants in an isolated population of the Adriatic coast of Croatia. | Zhang G et al. | β | 2011 | β |
| Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. | Soler Artigas M et al. | β | 2011 | β |
| Genome-wide association studies establish that human intelligence is highly heritable and polygenic. | Davies G et al. | β | 2011 | β |
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