Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion.
Nat Genet
; 45(2): 197-201, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-23263489
ABSTRACT
Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion; however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.5-5%) and rare (MAF < 0.5%) nonsynonymous variants, we analyzed exome array data in 8,229 nondiabetic Finnish males using the Illumina HumanExome Beadchip. We identified low-frequency coding variants associated with fasting proinsulin concentrations at the SGSM2 and MADD GWAS loci and three new genes with low-frequency variants associated with fasting proinsulin or insulinogenic index TBC1D30, KANK1 and PAM. We also show that the interpretation of single-variant and gene-based tests needs to consider the effects of noncoding SNPs both nearby and megabases away. This study demonstrates that exome array genotyping is a valuable approach to identify low-frequency variants that contribute to complex traits.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Variation
/
Exome
/
Insulin
Type of study:
Prognostic_studies
Limits:
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2013
Document type:
Article
Affiliation country:
United States