Genetic variants at 2q24 are associated with susceptibility to type 2 diabetes.
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.
Qi
Lu
L
Department of Nutrition, Harvard School of Public Health, and Brigham and Women's Hospital, Boston, MA, USA. nhlqi@channing.harvard.edu
Cornelis
Marilyn C
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Kraft
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Stanya
Kristopher J
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Linda Kao
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Pankow
James S
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Dupuis
Josée
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Florez
Jose C
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Fox
Caroline S
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Paré
Guillaume
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Cynthia J
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Laurie
Cathy C
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Mirel
Daniel B
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Teri A
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Chasman
Daniel I
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Boerwinkle
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David J
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James B
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Chih-Hao
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Frank B
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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*
D004268:DNA-Binding Proteins; D039641:Integrin beta Chains; C086384:RBMS1 protein, human; D016601:RNA-Binding Proteins; C072170:integrin beta6; D005947:Glucose