Genomic inflation factors under polygenic inheritance

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, Maegi, 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. and Visscher, Peter M. (2011) Genomic inflation factors under polygenic inheritance. European Journal of Human Genetics, 19 7: 807-812. doi:10.1038/ejhg.2011.39

Author 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
Maegi, 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.
Title Genomic inflation factors under polygenic inheritance
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1018-4813
Publication date 2011-07
Year available 2011
Sub-type Article (original research)
DOI 10.1038/ejhg.2011.39
Open Access Status
Volume 19
Issue 7
Start page 807
End page 812
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2011
Language eng
Formatted abstract
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. 
Keyword Genome wide association study
Genomic inflation factor
Polygenic inheritance
Population Stratification
Missing Heritability
Human Height
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 108 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 110 times in Scopus Article | Citations
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