Polygenic risk score for type 2 diabetes shows context-dependent effects across populations
Abstract
Abstract Polygenic risk scores hold prognostic value for identifying individuals at higher risk of type 2 diabetes. However, further characterization is needed to understand the generalizability of type 2 diabetes polygenic risk scores in diverse populations across various contexts. We systematically characterize a multi-ancestry type 2 diabetes polygenic risk score among 244,637 cases and 637,891 controls across diverse populations from the Population Architecture Genomics and Epidemiology Study and 13 additional biobanks and cohorts. Polygenic risk score performance is context dependent, with better performance in those who are younger, male, without hypertension, and not obese or overweight. Additionally, the polygenic risk score is associated with various diabetes-related cardiometabolic traits and type 2 diabetes complications, suggesting its utility for stratifying risk of complications and identifying shared genetic architecture between type 2 diabetes and other diseases. These findings highlight the need to account for context when evaluating polygenic risk score as a tool for type 2 diabetes risk prognostication and the potentially generalizable associations of type 2 diabetes polygenic risk score with diabetes-related traits, despite differential performance in type 2 diabetes prediction across diverse populations. Our study provides a comprehensive resource to characterize a type 2 diabetes polygenic risk score.
Article Details
Authors (153)
Boya Guo
Yanwei Cai
DaeEun Kim
Roelof A. J. Smit
Zhe Wang
Kruthika R. Iyer
Austin T. Hilliard
Jeffrey Haessler
Ran Tao
K. Alaine Broadaway
Yujie Wang
Shenyang National Laboratory for Materials Science, Institute of Metal Research
Nikita Pozdeyev
Frederik F. Stæger
Chaojie Yang
Brett Vanderwerff
Amit D. Patki
Lauren Stalbow
Meng Lin
Nicholas Rafaels
University of Colorado at Denver, Denver, CO, USA.
Jonathan Shortt
Laura Wiley
Maggie Stanislawski
Jack Pattee
Lea Davis
Peter S. Straub
Megan M. Shuey
Nancy J. Cox
Nanette R. Lee
Marit E. Jørgensen
Peter Bjerregaard
Christina Larsen
Torben Hansen
Ida Moltke
James B. Meigs
Daniel O. Stram
Xianyong Yin
Xiang Zhou
Kyong-Mi Chang
Shoa L. Clarke
Rodrigo Guarischi-Sousa
Joanna Lankester
Philip S. Tsao
Steven Buyske
Mariaelisa Graff
Laura M. Raffield
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Quan Sun
Lynne R. Wilkens
Christopher S. Carlson
Charles B. Easton
Simin Liu
Brown University, Providence, RI, USA.
JoAnn E. Manson
Loïc L. Marchand
Christopher A. Haiman
Karen L. Mohlke
Penny Gordon-Larsen
Anders Albrechtsen
Michael Boehnke
Stephen S. Rich
Department of Genome Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Ani Manichaikul
Department of Genome Sciences, Center for Public Health Genomics, University of Virginia
Jerome I. Rotter
Noha A. Yousri
Ryan M. Irvin
Heather D. Anderson
Christina L. Aquilante
Kelsey Arbogast
Christopher H. Arehart
Ian M. Brooks
Tonya M. Brunetti
Judith Brutus-Lestin
Elizabeth E. Burke
Emily M. Casteel
Joanne B. Cole
Curtis R. Coughlin
Kristy Crooks
Jacob Crawford
Erin Culver
Michelle N. Edelmann
Matthew J. Fisher
Alan W. Franklin
Teresa C. Frye
Hunter George
Elizabeth K. Gilliland
Casey S. Greene
Brooke Hawkes
Emily Hearst
Audrey E. Hendricks
Randi K. Johnson
Colleen G. Julian
Dave Kao
Iain Konigsberg
Lisa Ku
Elizabeth L. Kudron
Rashawnda Lacy
Ethan M. Lange
Yee Ming Lee
Joe A. Lesny
Jan T. Lowery
Luciana B. Vargas
Betzaida L. Maldonado
Darcy Marceau
James L. Martin
Brianna L. Gates
David Mayer
Nicole L. McDaniel
Andrew Monte
Ethan Moore
Ann Nadrash
Alaa Radwan
Nick Rafaels
Neda Rasouli
Elise L. Shalowitz
Hoda Sherif
Johnathan Shortt
Adrian M. Stewart
Kristen J. Sutton
Carolyn T. Swartz
Anna Tanaka
Matthew R. G. Taylor
Department of Medicine, Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Candace Teague
Emily B. Todd
Katy E. Trinkley
Laura K. Wiley
Sumitra Muralidhar
Jennifer Moser
Jennifer E. Deen
J. Michael Gaziano
Elizabeth Hauser
Amy Kilbourne
Michael Matheny
Dave Oslin
Deepak Voora
Jessica V. Brewer
Mary T. Brophy
Kelly Cho
Million Veteran Program Coordinating Center
Lori Churby
Scott L. DuVall
Saiju Pyarajan
Robert Ringer
Luis E. Selva
Shahpoor Alex Shayan
Brady Stephens
Stacey B. Whitbourne
Adriana Hung
Henry Kranzler
Chris Gignoux
Stanford University, Stanford, CA, USA.
Kari E. North
Ruth J. F. Loos
Themistocles L. Assimes
Ulrike Peters
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Charles Kooperberg
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Sridharan Raghavan
Heather M. Highland
Burcu F. Darst