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http://bura.brunel.ac.uk/handle/2438/13432
Title: | Analysis with the exome array identifies multiple new independent variants in lipid loci |
Authors: | Kanoni, S Masca, NGD Stirrups, KE Varga, TV Warren, HR Scott, RA Southam, L Zhang, W Yaghootkar, H Müller-Nurasyid, M Couto Alves, A Strawbridge, RJ Lataniotis, L Hashim, NAN Besse, C Boland, A Braund, PS Connell, JM Dominiczak, A Farmaki, A-E Franks, S Grallert, H Jansson, J-H 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, AIF Dedoussis, G Escher, SA Kooner, JS McCarthy, MI Palmer, CNA Hamsten, A Caulfield, MJ Frayling, TM Tobin, MD Jarvelin, M-R Zeggini, E Gieger, C Chambers, JC Wareham, NJ Munroe, PB Franks, PW Samani, NJ Deloukas, P |
Issue Date: | 2016 |
Citation: | Human Molecular Genetics, 2016, pp. ddw227 - ddw227 |
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. |
URI: | http://bura.brunel.ac.uk/handle/2438/13432 |
DOI: | http://dx.doi.org/10.1093/hmg/ddw227 |
ISSN: | 0964-6906 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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