美国密歇根大学Stephen C. J. Parker小组宣布他们研制了TOPMed中数量性状位点表达与剪接的交叉队列分析。相关论文于2026年7月16日发表在《科学》杂志上。

为了了解基因表达变异性的遗传学基础，该课题组对来自Trans-Omics for Precision Medicine项目的14324个RNA测序样本进行了特征分析，并在6种组织和细胞类型中进行了表达和剪接数量性状位点（e/sQTL）分析，包括全血（n = 6454）和肺（n = 1291）。课题组人员检测到数万个次级顺-e/sQTL，表明次级顺-e/sQTL的发现仍然是不饱和的。小组对来自164个性状的英国生物银行衍生的全基因组关联研究（GWAS）信号进行了精细定位，发现了10,611个GWAS信号的e/sQTL共定位，其中7096个信号与次级e/sQTL共定位。他们的结果表明，更大的e/sQTL分析将发现额外的次级e/sQTL，进一步有利于GWAS解释。

研究人员表示，大多数与复杂性状相关的遗传变异被假设为调节基因表达。

附：英文原文

Title: Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed

Author: Peter Orchard, Thomas W. Blackwell, Linda Kachuri, Peter J. Castaldi, Michael H. Cho, Stephanie A. Christenson, Peter Durda, Stacey Gabriel, Craig P. Hersh, Scott Huntsman, Seungyong Hwang, Roby Joehanes, Mari Johnson, Xingnan Li, Honghuang Lin, Ching-Ti Liu, Yongmei Liu, Angel C. Y. Mak, Ani W. Manichaikul, David T. Paik, Aabida Saferali, Joshua D. Smith, Kent D. Taylor, Russell P. Tracy, Jiongming Wang, Mingqiang Wang, Joshua S. Weinstock, Jeffrey Weiss, Heather E. Wheeler, Ying Zhou, Sebastian Zllner, Joseph C. Wu, Luisa Mestroni, Sharon Graw, Matthew R. G. Taylor, Victor E. Ortega, W. Craig Johnson, Weiniu Gan, Goncalo Abecasis, Deborah A. Nickerson, Namrata Gupta, Kristin Ardlie, Prescott G. Woodruff, Russell P. Bowler, Deborah A. Meyers, Alex Reiner, Charles Kooperberg, Elad Ziv, Ramachandran S. Vasan, Martin G. Larson, L. Adrienne Cupples, Edwin K. Silverman, Stephen S. Rich, Nancy Heard-Costa, Hua Tang, Jerome I. Rotter, Albert V. Smith, Daniel Levy, NHLBI TOPMed Consortium Multi-Omics Working Group, NHLBI TOPMed Consortium§, Franois Aguet, Laura J. Scott, Laura M. Raffield, Stephen C. J. Parker, Namiko Abe, Laura Almasy, Seth Ament, Pramod Anugu, Paul Auer, Dimitrios Avramopoulos, Adithya Balasubramanian, R. Graham Barr, Lucas Barwick, Terri Beaty, Diane Becker, Lewis Becker, Amber Beitelshees, Takis Benos, Marcos Bezerra, Joshua Bis, Jennifer Brody, Ulrich Broeckel, Jai Broome, Karen Bunting, Erin Buth, Vincent Carey, Cara Carty, Richard Casaburi, Mark Chaffin, Christy Chang, Yi-Cheng Chang, Sameer Chavan, Bo-Juen Chen, Wei-Min Chen, Seung Hoan Choi, Lee-Ming Chuang, Ren-Hua Chung, Matthew Conomos, Elaine Cornell, Carolyn Crandall, James Crapo, Jeffrey Curtis, Coleen Damcott, Sean David, Lisa de las Fuentes, Paul de Vries, Ranjan Deka, Dawn DeMeo, Scott Devine, Huyen Dinh, Harsha Doddapaneni, Qing Duan, Ravi Duggirala, Charles Eaton, Lynette Ekunwe, Adel El Boueiz, Leslie Emery, Charles Farber, Jesse Farek, Nora Franceschini, Chris Frazar, Mao Fu, Stephanie M. Fullerton, Lucinda Fulton, Shanshan Gao, Yan Gao, Margery Gass, Heather Geiger, Auyon Ghosh, Chris Gignoux, David Glahn, Stephanie Gogarten, Da-Wei Gong, Harald Goring, Daniel Grine, C. Charles Gu, Yue Guan, Michael Hall, Yi Han, Daniel Harris, Ben Heavner, David Herrington, Brian Hobbs, Elliott Hong, Karin Hoth, Chao (Agnes) Hsiung, Jianhong Hu, Yi-Jen Hung, Haley Huston, Chii Min Hwu

Issue&Volume: 2026-07-16

Abstract: 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.

DOI: adx2989

Source: https://www.science.org/doi/10.1126/science.adx2989

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

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