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Recent advances in understanding the genetic architecture of type 2 diabetes.


ABSTRACT: Genome-wide association (GWAS) and sequencing studies are providing new insights into the genetic basis of type 2 diabetes (T2D) and the inter-individual variation in glycemic traits, including levels of glucose, insulin, proinsulin and hemoglobin A1c (HbA1c). At the end of 2011, established loci (P < 5 × 10(-8)) totaled 55 for T2D and 32 for glycemic traits. Since then, most new loci have been detected by analyzing common [minor allele frequency (MAF)>0.05] variants in increasingly large sample sizes from populations around the world, and in trans-ancestry studies that successfully combine data from diverse populations. Most recently, advances in sequencing have led to the discovery of four loci for T2D or glycemic traits based on low-frequency (0.005 < MAF ? 0.05) variants, and additional low-frequency, potentially functional variants have been identified at GWAS loci. Established published loci now total ?88 for T2D and 83 for one or more glycemic traits, and many additional loci likely remain to be discovered. Future studies will build on these successes by identifying additional loci and by determining the pathogenic effects of the underlying variants and genes.

SUBMITTER: Mohlke KL 

PROVIDER: S-EPMC4572004 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Recent advances in understanding the genetic architecture of type 2 diabetes.

Mohlke Karen L KL   Boehnke Michael M  

Human molecular genetics 20150709 R1


Genome-wide association (GWAS) and sequencing studies are providing new insights into the genetic basis of type 2 diabetes (T2D) and the inter-individual variation in glycemic traits, including levels of glucose, insulin, proinsulin and hemoglobin A1c (HbA1c). At the end of 2011, established loci (P < 5 × 10(-8)) totaled 55 for T2D and 32 for glycemic traits. Since then, most new loci have been detected by analyzing common [minor allele frequency (MAF)>0.05] variants in increasingly large sample  ...[more]

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