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Because genes are believed to influence traits via gene expression, it is of interest to combine information from expression Quantitative Trait Loci (eQTLs) in a gene or genes in the same pathway. Such methods, widely referred to as transcriptomic wide association studies (TWAS), already exist for gene analysis. Due to the possibility of eliminating most of the confounding effects of linkage disequilibrium (LD) from TWAS gene statistics, pathway TWAS methods would be very useful in uncovering the true molecular basis of psychiatric disorders. However, such methods are not yet available for arbitrarily large pathways\/gene sets. This is possibly due to the quadratic (as a function of the number of SNPs) computational burden for computing LD across large chromosomal regions. To overcome this obstacle, we propose JEPEGMIX2\u2010P, a novel TWAS pathway method that (a) has a linear computational burden, (b) uses a large and diverse reference panel (33\u2009K subjects), (c) is competitive (adjusts for background enrichment in gene TWAS statistics), and (d) is applicable as\u2010is to ethnically mixed\u2010cohorts. To underline its potential for increasing the power to uncover genetic signals over the commonly used nontranscriptomics methods, for example,\n                    <jats:italic>MAGMA<\/jats:italic>\n                    , we applied JEPEGMIX2\u2010P to summary statistics of most large meta\u2010analyses from Psychiatric Genetics Consortium (PGC). While our work is just the very first step toward clinical translation of psychiatric disorders, PGC anorexia results suggest a possible avenue for treatment.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.b.32823","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T06:45:49Z","timestamp":1600670749000},"page":"454-463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["<scp>TWAS<\/scp>\n                    pathway method greatly enhances the number of leads for uncovering the molecular underpinnings of psychiatric disorders"],"prefix":"10.1002","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8997-6488","authenticated-orcid":false,"given":"Chris","family":"Chatzinakos","sequence":"first","affiliation":[{"name":"Mclean Hospital Harvard University  Cambridge Massachusetts USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foivos","family":"Georgiadis","sequence":"additional","affiliation":[{"name":"Mclean Hospital Harvard University  Cambridge Massachusetts USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Statistics University of Miami  Oxford Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Cai","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, Helmholtz Pioneer Campus  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir I.","family":"Vladimirov","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7139-7007","authenticated-orcid":false,"given":"Anna","family":"Docherty","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Utah  Salt Lake Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-5366","authenticated-orcid":false,"given":"Bradley T.","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brien P.","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Flint","sequence":"additional","affiliation":[{"name":"Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth S.","family":"Kendler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos P.","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"Mclean Hospital Harvard University  Cambridge Massachusetts USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviu\u2010Alin","family":"Bacanu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Virginia Commonwealth University  Richmond Virginia 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