Estimation of the multiple testing burden for genomewide association studies of nearly all common variants

By Itsik Pe'er, Roman Yelensky, David Altshuler, Mark J. Daly. Genetic Epidemiology, 2008

844 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/3e9506ae61cd06b3412b0b3dcb0f49ec07dd05e2

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In Genetics

Citations in the corpus

Common variants at 30 loci contribute to polygenic dyslipidemia (2008, neutral): “05 after adjusting for ∼1 million independent tests, the estimated multiple testing burden in GWAS of individuals of European ancestr”
Replication in genome-wide association studies (2009, background): “Empirical estimates of the threshold needed to preserve the genome-wide Type I error rate in studies of European-ancestry subjects using current genotyping arrays range from 5× 10 to 1× 10 [18, 24, 51, 59].”
Multiple common variants for celiac disease influencing immune gene expression (2010, neutral): “Finnish controls (12) were genotyped on the 610-Quad BeadChip; other samples were genotyped”
Meta-analyses of genome-wide association studies identify multiple novel loci associated with pulmonary function (2009, background): “The genome-wide significance threshold was defined a priori as P −8 , the Bonferroni adjustment for 1 million independent test”
Genetic Loci Influencing C-reactive Protein Levels and Risk of Coronary Heart Disease (2009, positive): “We used P 5 10 to designate genome-wide significance, taking account of the approximately1million independent tests forcommonvariantsacrossthegenome.(23) For5geneticlociassociatedwithCRPlevels at genome-wide significance, we selected the single most closely associated SNP (ie, smallest P value) for ”
Genome-wide association studies in ancestrally diverse populations: opportunities, methods, pitfalls, and recommendations. (2019, methodology): “Currently recommended significance thresholds range from 6 × 10−7 to 6 × 10−9 depending on allele frequency threshold, imputation panel, and ancestry of the GWAS, as well as the method used to estimate the appropriate threshold (Kanai et al., 2016; Li et al., 2012; Pe’er et al., 2008).”
Meta-analysis methods for genome-wide association studies and beyond (2013, methodology): “This roughly corresponds to a simple Bonferroni correction to maintain a 5% genome-wide type I error rate that is based on an estimated burden of 1 million independent comparisons for common sequence variation 18,43 .”
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (2010, neutral): “Follow-up of 25 lead SNPs in up to 76,558 additional individuals of European ancestry identified nine novel genome-wide significant associations (empirically determined as P 5×10 −8 )19 with FG and one with FI/HOMA-IR.”
Genome-wide Analysis of Genetic Loci Associated with Alzheimer’s Disease (2010, result): “7 10, which gives, for a 3-stage sequential analysis, the same control of false-positives as a single study’s use of P 5 10.(18) The 3 stages of meta-analyses were completed in May to August 2009.”
Statistical significance: p value, 0.05 threshold, and applications to radiomics—reasons for a conservative approach (2020, methodology): “05 threshold after the Bonferroni correction [29, 30], not from an arbitrary reduction.”