TY - JOUR
T1 - Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes
AU - Lohmueller, Kirk E.
AU - Sparsø, Thomas Hempel
AU - Li, Qibin
AU - Galijatovic, Ehm Astrid Andersson
AU - Korneliussen, Thorfinn Sand
AU - Albrechtsen, Anders
AU - Banasik, Karina
AU - Grarup, Niels
AU - Hallgrimsdottir, Ingileif
AU - Kiil, Kristoffer
AU - Oskari Kilpeläinen, Tuomas
AU - Krarup, Nikolaj Thure
AU - Pers, Tune Hannes
AU - Sanchez, Gaston
AU - Hu, Youna
AU - DeGiorgio, Michael
AU - Jørgensen, Torben
AU - Sandbæk, Annelli
AU - Lauritzen, Torsten
AU - Brunak, Søren
AU - Kristiansen, Karsten
AU - Li, Yingrui
AU - Hansen, Torben
AU - Wang, Jun
AU - Nielsen, Rasmus
AU - Pedersen, Oluf Borbye
N1 - Erratum: Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes DOI: 10.1016/j.ajhg.2014.02.002
PY - 2013/12/5
Y1 - 2013/12/5
N2 - 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/m(2) 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.
AB - 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/m(2) 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.
UR - http://10.1016/j.ajhg.2014.02.002
U2 - 10.1016/j.ajhg.2013.11.005
DO - 10.1016/j.ajhg.2013.11.005
M3 - Journal article
C2 - 24290377
VL - 93
SP - 1072
EP - 1086
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 6
ER -