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

Kirk E. Lohmueller, Thomas Sparsø, Qibin Li, Ehm Andersson, Thorfinn Korneliussen, Anders Albrechtsen, Karina Banasik, Niels Grarup, Ingileif Hallgrimsdottir, Kristoffer Kiil, Tuomas O. Kilpeläinen, Nikolaj T. Krarup, Tune H. Pers, Gaston Sanchez, Youna Hu, Michael Degiorgio, Torben Jørgensen, Annelli Sandbæk, Torsten Lauritzen, Søren BrunakKarsten Kristiansen, Yingrui Li, Torben Hansen, Jun Wang, Rasmus Nielsen, Oluf Pedersen

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1072-1086
Number of pages15
JournalAmerican Journal of Human Genetics
Issue number6
StatePublished - Dec 5 2013

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes'. Together they form a unique fingerprint.

Cite this