@article{c35cdf9c858d4e879ccb64b9a75718f9,
title = "Transcriptomic signatures across human tissues identify functional rare genetic variation",
abstract = "Rare genetic variants are abundant across the human genome, and identifying their function and phenotypic impact is a major challenge. Measuring aberrant gene expression has aided in identifying functional, large-effect rare variants (RVs). Here, we expanded detection of genetically driven transcriptome abnormalities by analyzing gene expression, allele-specific expression, and alternative splicing from multitissue RNA-sequencing data, and demonstrate that each signal informs unique classes of RVs. We developed Watershed, a probabilistic model that integrates multiple genomic and transcriptomic signals to predict variant function, validated these predictions in additional cohorts and through experimental assays, and used them to assess RVs in the UK Biobank, the Million Veterans Program, and the Jackson Heart Study. Our results link thousands of RVs to diverse molecular effects and provide evidence to associate RVs affecting the transcriptome with human traits.",
author = "{TOPMed Lipids Working Group} and {GTEx Consortium} and Ferraro, {Nicole M.} and Strober, {Benjamin J.} and Jonah Einson and Abell, {Nathan S.} and Francois Aguet and Barbeira, {Alvaro N.} and Margot Brandt and Maja Bucan and Castel, {Stephane E.} and Davis, {Joe R.} and Emily Greenwald and Hess, {Gaelen T.} and Hilliard, {Austin T.} and Kember, {Rachel L.} and Bence Kotis and Park, {Yo Son} and Gina Peloso and Shweta Ramdas and Scott, {Alexandra J.} and Craig Smail and Tsang, {Emily K.} and Zekavat, {Seyedeh M.} and Marcello Ziosi and Aradhana and Ardlie, {Kristin G.} and Assimes, {Themistocles L.} and Bassik, {Michael C.} and Brown, {Christopher D.} and Adolfo Correa and Ira Hall and Im, {Hae Kyung} and Xin Li and Pradeep Natarajan and Tuuli Lappalainen and Pejman Mohammadi and Montgomery, {Stephen B.} and Alexis Battle and Shankara Anand and Stacey Gabriel and Getz, {Gad A.} and Aaron Graubert and Kane Hadley and Handsaker, {Robert E.} and Huang, {Katherine H.} and Seva Kashin and Xiao Li and MacArthur, {Daniel G.} and Meier, {Samuel R.} and Nedzel, {Jared L.} and Conrad, {Donald F.}",
note = "Publisher Copyright: {\textcopyright} 2020 American Association for the Advancement of Science. All rights reserved.",
year = "2020",
month = sep,
day = "11",
doi = "10.1126/science.aaz5900",
language = "English (US)",
volume = "369",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6509",
}