Student and Faculty Publications

Authors

Rebecca Keener
Surya B Chhetri
Carla J Connelly
Margaret A Taub
Matthew P Conomos
Joshua Weinstock
Bohan Ni
Benjamin Strober
Stella Aslibekyan
Paul L Auer
Lucas Barwick
Lewis C Becker
John Blangero
Eugene R Bleecker
Jennifer A Brody
Brian E Cade
Juan C Celedon
Yi-Cheng Chang
L Adrienne Cupples
Brian Custer
Barry I Freedman
Mark T Gladwin
Susan R Heckbert
Lifang Hou
Marguerite R Irvin
Carmen R Isasi
Jill M Johnsen
Eimear E Kenny
Charles Kooperberg
Ryan L Minster
Take Naseri
Satupa'itea Viali
Sergei Nekhai
Nathan Pankratz
Patricia A Peyser
Kent D Taylor
Marilyn J Telen
Baojun Wu
Lisa R Yanek
Ivana V Yang
Christine Albert
Donna K Arnett
Allison E Ashley-Koch
Kathleen C Barnes
Joshua C Bis
Thomas W Blackwell
Eric Boerwinkle
Esteban G Burchard
April P Carson
Zhanghua Chen
Yii-Der Ida Chen
Dawood Darbar
Mariza de Andrade
Patrick T Ellinor
Myriam Fornage
Bruce D Gelb
Frank D Gilliland
Jiang He
Talat Islam
Stefan Kaab
Sharon L R Kardia
Shannon Kelly
Barbara A Konkle
Rajesh Kumar
Ruth J F Loos
Fernando D Martinez
Stephen T McGarvey
Deborah A Meyers
Braxton D Mitchell
Courtney G Montgomery
Kari E North
Nicholette D Palmer
Juan M Peralta
Benjamin A Raby
Susan Redline
Stephen S Rich
Dan Roden
Jerome I Rotter
Ingo Ruczinski
David Schwartz
Frank Sciurba
M Benjamin Shoemaker
Edwin K Silverman
Moritz F Sinner
Nicholas L Smith
Albert V Smith
Hemant K Tiwari
Ramachandran S Vasan
Scott T Weiss
L Keoki Williams
Yingze Zhang
Elad Ziv
Laura M Raffield
Alexander P Reiner
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
TOPMed Hematology and Hemostasis Working Group
TOPMed Structural Variation Working Group
Marios Arvanitis
Carol W Greider
Rasika A Mathias
Alexis Battle

Publication Date

5-24-2024

Journal

Nature Communications

Abstract

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

Keywords

Humans, Genome-Wide Association Study, Telomere, K562 Cells, Telomere Homeostasis, Polymorphism, Single Nucleotide, Gene Expression Regulation, CRISPR-Cas Systems

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