Abstract
To correct for a large number of hypothesis tests, most researchers rely on simple multiple testing corrections. Yet, new methodologies of selective inference could potentially improve power while retaining statistical guarantees, especially those that enable exploration of test statistics using auxiliary information (covariates) to weight hypothesis tests for association. We explore one such method, adaptive P-value thresholding (AdaPT), in the framework of genome-wide association studies (GWAS) and gene expression/coexpression studies, with particular emphasis on schizophrenia (SCZ). Selected SCZ GWAS association P values play the role of the primary data for AdaPT; single-nucleotide polymorphisms (SNPs) are selected because they are gene expression quantitative trait loci (eQTLs). This natural pairing of SNPs and genes allow us to map the following covariate values to these pairs: GWAS statistics from genetically correlated bipolar disorder, the effect size of SNP genotypes on gene expression, and gene-gene coexpression, captured by subnetwork (module) membership. In all, 24 covariates per SNP/gene pair were included in the AdaPT analysis using flexible gradient boosted trees. We demonstrate a substantial increase in power t...Continue Reading
References
May 10, 2000·Nature Genetics·M AshburnerG Sherlock
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Bin Zhang, Steve Horvath
Jan 20, 2009·Lancet·Paul LichtensteinChristina M Hultman
Apr 14, 2010·PLoS Genetics·Antonella GalliRolf Zeller
Jul 10, 2010·Bioinformatics·Cristen J WillerGonçalo R Abecasis
Aug 13, 2013·Nature Genetics·UNKNOWN Cross-Disorder Group of the Psychiatric Genomics ConsortiumUNKNOWN International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)
Nov 28, 2013·Molecular Psychiatry·Douglas M RuderferKenneth S Kendler
Jul 25, 2014·Nature·UNKNOWN Schizophrenia Working Group of the Psychiatric Genomics Consortium
Feb 13, 2015·Nature·Adam E LockeElizabeth K Speliotes
May 9, 2015·Science·UNKNOWN GTEx Consortium
Feb 9, 2016·Journal of the American Statistical Association·James G ScottRobert E Kass
May 31, 2016·Nature Methods·Nikolaos IgnatiadisWolfgang Huber
Jun 18, 2017·Cell·Evan A BoyleJonathan K Pritchard
Jan 26, 2018·PloS One·Min ZhangVictor H Guaiquil
Feb 7, 2018·Nature Communications·Rebecca E KochGeoffrey E Hill
Jun 16, 2018·Cell·UNKNOWN Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Electronic address: douglas.ruderfe, UNKNOWN Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium
Oct 10, 2018·Nature Genetics·Anubha MahajanMark I McCarthy
Nov 6, 2018·Nucleic Acids Research·UNKNOWN The Gene Ontology Consortium
Dec 26, 2018·PeerJ·Simina M Boca, Jeffrey T Leek
Jun 6, 2019·Genome Biology·Keegan KorthauerStephanie C Hicks
Aug 2, 2019·Nature Communications·Martin J ZhangJames Zou
Aug 14, 2019·American Journal of Human Genetics·Luke J O'ConnorAlkes L Price
Apr 9, 2020·Cell Reports·Donna M WerlingNenad Sestan
Citations
Nov 21, 2020·Neurotoxicity Research·Ling-Zhi MaJin-Tai Yu
Jun 10, 2021·PloS One·Otília MenyhartBalázs Győrffy
Jul 2, 2021·Nucleic Acids Research·Elisa SalviatoFrancesco Ferrari
Aug 31, 2021·Briefings in Bioinformatics·Ronald YurkoMax G'Sell
Oct 21, 2021·PLoS Genetics·Anna HutchinsonChris Wallace