Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps.

Nat Genet 2016 11 26;48(11):1303-1312. Epub 2016 Sep 26.

Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low-frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279872PMC
November 2016
97 Reads
29.350 Impact Factor

Publication Analysis

Top Keywords

whole-genome sequence
8
cardiometabolic hematological
8
loci associated
8
sequence data
8
function findings
4
rare minor
4
improve understanding
4
including rare
4
associations including
4
minor allele
4
maf variants
4
allele frequency
4
frequency maf
4
low-frequency maf
4
understanding allelic
4
findings improve
4
maf low-frequency
4
traits describe
4
sets fewer
4
european ancestry
4

References

(Supplied by CrossRef)
Article in Science
JC Cohen et al.
Science 2004
Article in Nat. Genet.
CT Johansen et al.
Nat. Genet. 2010
Article in Nat. Genet.
PL Auer et al.
Nat. Genet. 2014
Article in Nat. Genet.
CJ Willer et al.
Nat. Genet. 2013
Article in Nat. Genet.
JR Huyghe et al.
Nat. Genet. 2013
Article in Nat. Genet.
AP Morris et al.
Nat. Genet. 2012
Article in Am. J. Hum. Genet.
GM Peloso et al.
Am. J. Hum. Genet. 2014
Article in Nature
P van der Harst et al.
Nature 2012
Article in Am. J. Hum. Genet.
PL Auer et al.
Am. J. Hum. Genet. 2012
Article in Nat. Genet.
V Steinthorsdottir et al.
Nat. Genet. 2014
Article in Nat. Genet.
I Surakka et al.
Nat. Genet. 2015

Similar Publications