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Cited by 282

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Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion

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Huyghe, Jeroen R, Jackson, Anne U, Fogarty, Marie P, Buchkovich, Martin L, Stančáková, Alena, Stringham, Heather M, Sim, Xueling, Yang, Lingyao, Fuchsberger, Christian, Cederberg, Henna, Chines, Peter S, Teslovich, Tanya M, Romm, Jane M, Ling, Hua, McMullen, Ivy, Ingersoll, Roxann, Pugh, Elizabeth W, Doheny, Kimberly F, Neale, Benjamin M, Daly, Mark J, Kuusisto, Johanna, Scott, Laura J, Kang, Hyun Min, Collins, Francis S, Abecasis, Gonçalo R, Watanabe, Richard M, Boehnke, Michael, Laakso, Markku, Mohlke, Karen L·2013·Nature Genetics
DOI 10.1038/ng.2507
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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.

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Research works printed but not linked: 35

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Metadata

Authors
Huyghe, J. R., Jackson, A. U., Fogarty, M. P., Buchkovich, M. L., Stančáková, A., Stringham, H. M., Sim, X., Yang, L., Fuchsberger, C., Cederberg, H., Chines, P. S., Teslovich, T. M., Romm, J. M., Ling, H., McMullen, I., Ingersoll, R., Pugh, E. W., Doheny, K. F., Neale, B. M., Daly, M. J., Kuusisto, J., Scott, L. J., Kang, H. M., Collins, F. S., Abecasis, G. R., Watanabe, R. M., Boehnke, M., Laakso, M., & Mohlke, K. L.
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2012-12-23
Volume
45
Issue
2
Pages
197-201
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.2507
OpenAlex
W2061604798
Cited by
282
References
10
FWCI
18.25
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. https://app.cochat.ai/papers/10.1038/ng.2507
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Huyghe, J. R., Jackson, A. U., Fogarty, M. P., Buchkovich, M. L., Stančáková, A., Stringham, H. M., Sim, X., Yang, L., Fuchsberger, C., Cederberg, H., Chines, P. S., Teslovich, T. M., Romm, J. M., Ling, H., McMullen, I., Ingersoll, R., Pugh, E. W., Doheny, K. F., Neale, B. M., . . . Mohlke, K. L. (2013). Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. Nature Genetics. https://doi.org/10.1038/ng.2507

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