| Literature DB >> 35530816 |
Margaret A Taub1, Matthew P Conomos2, Rebecca Keener3, Kruthika R Iyer4, Joshua S Weinstock5,6, Lisa R Yanek7, John Lane8, Tyne W Miller-Fleming9, Jennifer A Brody10, Laura M Raffield11, Caitlin P McHugh2, Deepti Jain2, Stephanie M Gogarten2, Cecelia A Laurie2, Ali Keramati12, Marios Arvanitis13, Albert V Smith5,6, Benjamin Heavner2, Lucas Barwick14, Lewis C Becker7, Joshua C Bis10, John Blangero15, Eugene R Bleecker16,17, Esteban G Burchard18,19, Juan C Celedón20, Yen Pei C Chang21, Brian Custer22,23, Dawood Darbar24, Lisa de Las Fuentes25, Dawn L DeMeo26,27, Barry I Freedman28, Melanie E Garrett29,30, Mark T Gladwin31, Susan R Heckbert32,33, Bertha A Hidalgo34, Marguerite R Irvin34, Talat Islam35, W Craig Johnson36, Stefan Kaab37,38, Lenore Launer39, Jiwon Lee40, Simin Liu41, Arden Moscati42, Kari E North43, Patricia A Peyser44, Nicholas Rafaels45, Christine Seidman46, Daniel E Weeks47,48, Fayun Wen49, Marsha M Wheeler50, L Keoki Williams51, Ivana V Yang45, Wei Zhao44, Stella Aslibekyan34, Paul L Auer52, Donald W Bowden53, Brian E Cade54,27, Zhanghua Chen35, Michael H Cho26, L Adrienne Cupples55,56, Joanne E Curran15, Michelle Daya45, Ranjan Deka57, Celeste Eng18, Tasha E Fingerlin58,59, Xiuqing Guo60, Lifang Hou61, Shih-Jen Hwang62, Jill M Johnsen63,64, Eimear E Kenny65,42, Albert M Levin66, Chunyu Liu56,67, Ryan L Minster47, Take Naseri68,69, Mehdi Nouraie31, Muagututi'a Sefuiva Reupena70, Ester C Sabino71, Jennifer A Smith44, Nicholas L Smith32,33, Jessica Lasky Su26,27, James G Taylor49, Marilyn J Telen29,72, Hemant K Tiwari73, Russell P Tracy74, Marquitta J White18, Yingze Zhang31, Kerri L Wiggins10, Scott T Weiss26,27, Ramachandran S Vasan75,56, Kent D Taylor60, Moritz F Sinner37,38, Edwin K Silverman26,27, M Benjamin Shoemaker76, Wayne H-H Sheu77, Frank Sciurba78, David A Schwartz45, Jerome I Rotter79, Daniel Roden80, Susan Redline54,81, Benjamin A Raby82,83, Bruce M Psaty84, Juan M Peralta15, Nicholette D Palmer53, Sergei Nekhai49, Courtney G Montgomery85, Braxton D Mitchell21,86, Deborah A Meyers16,17, Stephen T McGarvey69, Angel Cy Mak18, Ruth Jf Loos42,87, Rajesh Kumar88, Charles Kooperberg89, Barbara A Konkle63,64, Shannon Kelly22,90, Sharon Lr Kardia44, Robert Kaplan91, Jiang He92, Hongsheng Gui51, Frank D Gilliland35, Bruce D Gelb93, Myriam Fornage94,95, Patrick T Ellinor96, Mariza de Andrade97, Adolfo Correa98, Yii-Der Ida Chen60, Eric Boerwinkle99, Kathleen C Barnes45, Allison E Ashley-Koch29,30, Donna K Arnett100, Cathy C Laurie2, Goncalo Abecasis5,101, Deborah A Nickerson50, James G Wilson102, Stephen S Rich103, Daniel Levy56,67, Ingo Ruczinski1, Abraham Aviv104, Thomas W Blackwell5,6, Timothy Thornton105, Jeff O'Connell106,107, Nancy J Cox108, James A Perry21, Mary Armanios109, Alexis Battle3,110, Nathan Pankratz8, Alexander P Reiner111,89, Rasika A Mathias7.
Abstract
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10-9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes.Entities:
Year: 2022 PMID： 35530816 PMCID： PMC9075703 DOI： 10.1016/j.xgen.2021.100084
Source DB: PubMed Journal: Cell Genom ISSN： 2666-979X