Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics
Genre
Journal ArticleDate
2018-12-01Author
Barbeira, ANDickinson, SP
Bonazzola, R
Zheng, J
Wheeler, HE
Torres, JM
Torstenson, ES
Shah, KP
Garcia, T
Edwards, TL
Stahl, EA
Huckins, LM
Aguet, F
Ardlie, KG
Cummings, BB
Gelfand, ET
Getz, G
Hadley, K
Handsaker, RE
Huang, KH
Kashin, S
Karczewski, KJ
Lek, M
Li, X
MacArthur, DG
Nedzel, JL
Nguyen, DT
Noble, MS
Segrè, AV
Trowbridge, CA
Tukiainen, T
Abell, NS
Balliu, B
Barshir, R
Basha, O
Battle, A
Bogu, GK
Brown, A
Brown, CD
Castel, SE
Chen, LS
Chiang, C
Conrad, DF
Damani, FN
Davis, JR
Delaneau, O
Dermitzakis, ET
Engelhardt, BE
Eskin, E
Ferreira, PG
Frésard, L
Gamazon, ER
Garrido-Martín, D
Gewirtz, ADH
Gliner, G
Gloudemans, MJ
Guigo, R
Hall, IM
Han, B
He, Y
Hormozdiari, F
Howald, C
Jo, B
Kang, EY
Kim, Y
Kim-Hellmuth, S
Lappalainen, T
Li, G
Li, X
Liu, B
Mangul, S
McCarthy, MI
McDowell, IC
Mohammadi, P
Monlong, J
Montgomery, SB
Muñoz-Aguirre, M
Ndungu, AW
Nobel, AB
Oliva, M
Ongen, H
Palowitch, JJ
Panousis, N
Papasaikas, P
Park, YS
Parsana, P
Payne, AJ
Peterson, CB
Quan, J
Reverter, F
Sabatti, C
Saha, A
Sammeth, M
Scott, AJ
Shabalin, AA
Sodaei, R
Stephens, M
Stranger, BE
Strober, BJ
Sul, JH
Subject
Chromosome MappingComputer Simulation
Gene Expression
Genetic Variation
Genome-Wide Association Study
Humans
Meta-Analysis as Topic
Models, Genetic
Organ Specificity
Phenotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Permanent link to this record
http://hdl.handle.net/20.500.12613/4666
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Show full item recordDOI
10.1038/s41467-018-03621-1Abstract
© 2018 The Author(s). Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease genes are enriched among significant associations for related traits, suggesting that smaller alterations of these genes may cause a spectrum of milder phenotypes.Citation to related work
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http://dx.doi.org/10.34944/dspace/4648