PuSH - Publikationsserver des Helmholtz Zentrums München

Kanoni, S.* ; Masca, N.G.D.* ; Stirrups, K.E.* ; Varga, T.V.* ; Warren, H.R.* ; Scott, R.A.* ; Southam, L.* ; Zhang, W.* ; Yaghootkar, H.* ; Müller-Nurasyid, M. ; Couto Alves, A.* ; Strawbridge, R.J.* ; Lataniotis, L.* ; Hashim, N.A.* ; Besse, C.* ; Boland, A.* ; Braund, P.S.* ; Connell, J.M.* ; Dominiczak, A.* ; Farmaki, A.-E.* ; Franks, S.* ; Grallert, H. ; Jansson, J.H.* ; Karaleftheri, M.* ; Keinanen-Kiukaanniemi, S.* ; Matchan, A.* ; Pasko, D.* ; Peters, A. ; Poulter, N.* ; Rayner, N.W.* ; Renström, F.* ; Rolandsson, O.* ; Sabater-Lleal, M.* ; Sennblad, B.* ; Sever, P.* ; Shields, D.* ; Silveira, A.* ; Stanton, A.V.* ; Strauch, K. ; Tomaszewski, M.* ; Tsafantakis, E.* ; Waldenberger, M. ; Blakemore, A.I.* ; Dedoussis, G.* ; Escher, S.A.* ; Kooner, J.S.* ; McCarthy, M.I.* ; Palmer, C.N.* ; Hamsten, A.* ; Caulfield, M.J.* ; Frayling, T.M.* ; Tobin, M.D.* ; Jarvelin, M.R.* ; Zeggini, E.* ; Gieger, C. ; Chambers, J.C.* ; Wareham, N.J.* ; Munroe, P.B.* ; Franks, P.W.* ; Samani, N.J.* ; Deloukas, P.*

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

Hum. Mol. Genet. 25, 4094-4106 (2016)
Verlagsversion Postprint DOI PMC
Open Access Green
It has been hypothesised that low frequency (1-5% 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 (6 had MAF < 5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1-5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5-2.5 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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Genome-wide Association; Coronary-artery-disease; Low-frequency; Ldl-cholesterol; Blood-lipids; Rare; Heritability; Metaanalysis; Transporter; Traits
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Zeitschrift Human Molecular Genetics
Quellenangaben Band: 25, Heft: 18, Seiten: 4094-4106 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)