title: Consistent directions of effect for established type 2 diabetes risk variants across populations: the population architecture using Genomics and Epidemiology (PAGE) Consortium.
abstract: Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (P(heterogeneity) < 0.05), eight were positively associated with risk (OR >1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA. haiman@usc.edu
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Megan D
authors.initials: MD
authors.lastname: Fesinmeyer
authors.forename: Kylee L
authors.initials: KL
authors.lastname: Spencer
authors.forename: Petra
authors.initials: P
authors.lastname: Buzková
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Peggy
authors.initials: P
authors.lastname: Wan
authors.forename: Jeff
authors.initials: J
authors.lastname: Haessler
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Monroe
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Steven
authors.initials: S
authors.lastname: Buyske
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goodloe
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Kevin
authors.initials: K
authors.lastname: Waters
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
authors.forename: Peter
authors.initials: P
authors.lastname: Shrader
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Ambite
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D056186:Metagenomics; D008875:Middle Aged; D044382:Population Groups / Q000235:genetics*; D012306:Risk; D012307:Risk Factors