title: Genetic variants at 2q24 are associated with susceptibility to type 2 diabetes.
abstract: To identify type 2 diabetes (T2D) susceptibility loci, we conducted genome-wide association (GWA) scans in nested case-control samples from two prospective cohort studies, including 2591 patients and 3052 controls of European ancestry. Validation was performed in 11 independent GWA studies of 10,870 cases and 73,735 controls. We identified significantly associated variants near RBMS1 and ITGB6 genes at 2q24, best-represented by SNP rs7593730 (combined OR=0.90, 95% CI=0.86-0.93; P=3.7x10(-8)). The frequency of the risk-lowering allele T is 0.23. Variants in this region were nominally related to lower fasting glucose and HOMA-IR in the MAGIC consortium (P<0.05). These data suggest that the 2q24 locus may influence the T2D risk by affecting glucose metabolism and insulin resistance.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, and Brigham and Women's Hospital, Boston, MA, USA. nhlqi@channing.harvard.edu
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Cornelis
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Kristopher J
authors.initials: KJ
authors.lastname: Stanya
authors.forename: W H
authors.initials: WH
authors.lastname: Linda Kao
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Girman
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mirel
authors.forename: Teri A
authors.initials: TA
authors.lastname: Manolio
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lee
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002889:Chromosomes, Human, Pair 2; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D039641:Integrin beta Chains / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D039641:Integrin beta Chains; C086384:RBMS1 protein, human; D016601:RNA-Binding Proteins; C072170:integrin beta6; D005947:Glucose