Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes

Lohmueller, Kirk E., Sparso, Thomas, Li, Qibin, Andersson, Ehm, Korneliussen, Thorfinn, Albrechtsen, Anders, Banasik, Karina, Grarup, Niels, Hallgrimsdottir, Ingileif, Kiil, Kristoffer, Kilpelainen, Tuomas O., Krarup, Nikolaj T., Pers, Tune H., Sanchez, Gaston, Hu, Youna, DeGiorgio, Michael, Jorgensen, Torben, Sandbaek, Annelli, Lauritzen, Torsten, Brunak, Soren, Kristiansen, Karsten, Li, Yingrui, Hansen, Torben, Wang, Jun, Nielsen, Rasmus and Pedersen, Oluf (2013) Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes. American Journal of Human Genetics, 93 6: 1072-1086. doi:10.1016/j.ajhg.2013.11.005

Author Lohmueller, Kirk E.
Sparso, Thomas
Li, Qibin
Andersson, Ehm
Korneliussen, Thorfinn
Albrechtsen, Anders
Banasik, Karina
Grarup, Niels
Hallgrimsdottir, Ingileif
Kiil, Kristoffer
Kilpelainen, Tuomas O.
Krarup, Nikolaj T.
Pers, Tune H.
Sanchez, Gaston
Hu, Youna
DeGiorgio, Michael
Jorgensen, Torben
Sandbaek, Annelli
Lauritzen, Torsten
Brunak, Soren
Kristiansen, Karsten
Li, Yingrui
Hansen, Torben
Wang, Jun
Nielsen, Rasmus
Pedersen, Oluf
Title Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2013-12-05
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2013.11.005
Open Access Status Not Open Access
Volume 93
Issue 6
Start page 1072
End page 1086
Total pages 15
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Abstract It has been hypothesized that, in aggregate, rare variants in coding regions of genes explain a substantial fraction of the heritability of common diseases. We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index > 27.5 kg/m2 and hypertension) and 1,000 healthy controls to an average depth of 56×. Our simulations suggest that our study had the statistical power to detect at least one causal gene (a gene containing causal mutations) if the heritability of these common diseases was explained by rare variants in the coding regions of a limited number of genes. We applied a series of gene-based tests to detect such susceptibility genes. However, no gene showed a significant association with disease risk after we corrected for the number of genes analyzed. Thus, we could reject a model for the genetic architecture of type 2 diabetes where rare nonsynonymous variants clustered in a modest number of genes (fewer than 20) are responsible for the majority of disease risk.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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