Altmetric

Analysis with the exome array identifies multiple new independent variants in lipid loci.

File Description SizeFormat 
Kanoni et al 2016 Hum. Mol. Genet.-2016-Kanoni-hmg_ddw227.pdfAccepted version315.78 kBAdobe PDFView/Open
Title: Analysis with the exome array identifies multiple new independent variants in lipid loci.
Authors: Kanoni, S
Masca, NG
Stirrups, KE
Varga, TV
Warren, HR
Scott, RA
Southam, L
Zhang, W
Yaghootkar, H
Müller-Nurasyid, M
Couto Alves, A
Strawbridge, RJ
Lataniotis, L
An Hashim, N
Besse, C
Boland, A
Braund, PS
Connell, JM
Dominiczak, A
Farmaki, AE
Franks, S
Grallert, H
Jansson, JH
Karaleftheri, M
Keinänen-Kiukaanniemi, S
Matchan, A
Pasko, D
Peters, A
Poulter, N
Rayner, NW
Renström, F
Rolandsson, O
Sabater-Lleal, M
Sennblad, B
Sever, P
Shields, D
Silveira, A
Stanton, AV
Strauch, K
Tomaszewski, M
Tsafantakis, E
Waldenberger, M
Blakemore, AI
Dedoussis, G
Escher, SA
Kooner, JS
McCarthy, MI
Palmer, CN
Wellcome Trust Case Control Consortium
Hamsten, A
Caulfield, MJ
Frayling, TM
Tobin, MD
Jarvelin, MR
Zeggini, E
Gieger, C
Chambers, JC
Wareham, NJ
Munroe, PB
Franks, PW
Samani, NJ
Deloukas, P
Item Type: Journal Article
Abstract: It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
Issue Date: 27-Jul-2016
Date of Acceptance: 8-Jul-2016
URI: http://hdl.handle.net/10044/1/40217
DOI: https://dx.doi.org/10.1093/hmg/ddw227
ISSN: 1460-2083
Publisher: Oxford University Press (OUP)
Start Page: 4094
End Page: 4106
Journal / Book Title: Human Molecular Genetics
Volume: 25
Issue: 18
Copyright Statement: Copyright © 2016, Oxford University Press
Sponsor/Funder: Medical Research Council (MRC)
National Institute for Health Research
MRC
Funder's Grant Number: G0802782
NF-SI-0513-10059
G0802782
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
GENOME-WIDE ASSOCIATION
CORONARY-ARTERY-DISEASE
LOW-FREQUENCY
LDL-CHOLESTEROL
BLOOD-LIPIDS
RARE
HERITABILITY
METAANALYSIS
TRANSPORTER
TRAITS
Adolescent
Adult
Aged
Child
Cholesterol, HDL
Cholesterol, LDL
European Continental Ancestry Group
Exome
Gene Frequency
Genome-Wide Association Study
Humans
Lipid Metabolism
Lipids
Middle Aged
Polymorphism, Single Nucleotide
Triglycerides
Wellcome Trust Case Control Consortium
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
National Heart and Lung Institute
Department of Medicine (up to 2019)
Faculty of Medicine
Epidemiology, Public Health and Primary Care



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons