TY - JOUR
T1 - Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed
AU - Orchard, Peter
AU - Blackwell, Thomas W.
AU - Kachuri, Linda
AU - Castaldi, Peter J.
AU - Cho, Michael H.
AU - Christenson, Stephanie A.
AU - Durda, Peter
AU - Gabriel, Stacey
AU - Hersh, Craig P.
AU - Huntsman, Scott
AU - Hwang, Seungyong
AU - Joehanes, Roby
AU - Johnson, Mari
AU - Li, Xingnan
AU - Lin, Honghuang
AU - Liu, Ching Ti
AU - Liu, Yongmei
AU - Mak, Angel C.Y.
AU - Manichaikul, Ani W.
AU - Paik, David T.
AU - Saferali, Aabida
AU - Smith, Joshua D.
AU - Taylor, Kent D.
AU - Tracy, Russell P.
AU - Wang, Jiongming
AU - Wang, Mingqiang
AU - Weinstock, Joshua S.
AU - Weiss, Jeffrey
AU - Wheeler, Heather E.
AU - Zhou, Ying
AU - Zöllner, Sebastian
AU - Wu, Joseph C.
AU - Mestroni, Luisa
AU - Graw, Sharon
AU - Taylor, Matthew R.G.
AU - Ortega, Victor E.
AU - Johnson, W. Craig
AU - Gan, Weiniu
AU - Abecasis, Goncalo
AU - Nickerson, Deborah A.
AU - Gupta, Namrata
AU - Ardlie, Kristin
AU - Woodruff, Prescott G.
AU - Bowler, Russell P.
AU - Meyers, Deborah A.
AU - Reiner, Alex
AU - Kooperberg, Charles
AU - Ziv, Elad
AU - Vasan, Ramachandran S.
AU - Larson, Martin G.
N1 - Publisher Copyright:
Copyright © 2026 The Authors, some rights reserved;
PY - 2026/7/16
Y1 - 2026/7/16
N2 - Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTl) analyses in six tissues and cell types, including whole blood (n = 6454) and lung (n = 1291). We detected tens of thousands of secondary cis-e/sQTls, showing that secondary cis-e/sQTl discovery remains unsaturated. We fine-mapped uK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTl colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTls. Our results suggest that even larger e/sQTl analyses will uncover additional secondary e/sQTls, further benefiting GWAS interpretation.
AB - Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTl) analyses in six tissues and cell types, including whole blood (n = 6454) and lung (n = 1291). We detected tens of thousands of secondary cis-e/sQTls, showing that secondary cis-e/sQTl discovery remains unsaturated. We fine-mapped uK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTl colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTls. Our results suggest that even larger e/sQTl analyses will uncover additional secondary e/sQTls, further benefiting GWAS interpretation.
UR - https://www.scopus.com/pages/publications/105045591152
U2 - 10.1126/science.adx2989
DO - 10.1126/science.adx2989
M3 - Journal article
C2 - 42462027
AN - SCOPUS:105045591152
SN - 0036-8075
VL - 393
JO - Science
JF - Science
IS - 6808
M1 - eadx2989
ER -