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@article{Kanoni:2016:hmg/ddw227,
author = {Kanoni, S and Masca, NG and Stirrups, KE and Varga, TV and Warren, HR and Scott, RA and Southam, L and Zhang, W and Yaghootkar, H and Müller-Nurasyid, M and Couto, Alves A and Strawbridge, RJ and Lataniotis, L and An, Hashim N and Besse, C and Boland, A and Braund, PS and Connell, JM and Dominiczak, A and Farmaki, AE and Franks, S and Grallert, H and Jansson, JH and Karaleftheri, M and Keinänen-Kiukaanniemi, S and Matchan, A and Pasko, D and Peters, A and Poulter, N and Rayner, NW and Renström, F and Rolandsson, O and Sabater-Lleal, M and Sennblad, B and Sever, P and Shields, D and Silveira, A and Stanton, AV and Strauch, K and Tomaszewski, M and Tsafantakis, E and Waldenberger, M and Blakemore, AI and Dedoussis, G and Escher, SA and Kooner, JS and McCarthy, MI and Palmer, CN and Wellcome, Trust Case Control Consortium and Hamsten, A and Caulfield, MJ and Frayling, TM and Tobin, MD and Jarvelin, MR and Zeggini, E and Gieger, C and Chambers, JC and Wareham, NJ and Munroe, PB and Franks,},
doi = {hmg/ddw227},
journal = {Human Molecular Genetics},
pages = {4094--4106},
title = {Analysis with the exome array identifies multiple new independent variants in lipid loci.},
url = {http://dx.doi.org/10.1093/hmg/ddw227},
volume = {25},
year = {2016}
}

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TY  - JOUR
AB  - 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.
AU  - Kanoni,S
AU  - Masca,NG
AU  - Stirrups,KE
AU  - Varga,TV
AU  - Warren,HR
AU  - Scott,RA
AU  - Southam,L
AU  - Zhang,W
AU  - Yaghootkar,H
AU  - Müller-Nurasyid,M
AU  - Couto,Alves A
AU  - Strawbridge,RJ
AU  - Lataniotis,L
AU  - An,Hashim N
AU  - Besse,C
AU  - Boland,A
AU  - Braund,PS
AU  - Connell,JM
AU  - Dominiczak,A
AU  - Farmaki,AE
AU  - Franks,S
AU  - Grallert,H
AU  - Jansson,JH
AU  - Karaleftheri,M
AU  - Keinänen-Kiukaanniemi,S
AU  - Matchan,A
AU  - Pasko,D
AU  - Peters,A
AU  - Poulter,N
AU  - Rayner,NW
AU  - Renström,F
AU  - Rolandsson,O
AU  - Sabater-Lleal,M
AU  - Sennblad,B
AU  - Sever,P
AU  - Shields,D
AU  - Silveira,A
AU  - Stanton,AV
AU  - Strauch,K
AU  - Tomaszewski,M
AU  - Tsafantakis,E
AU  - Waldenberger,M
AU  - Blakemore,AI
AU  - Dedoussis,G
AU  - Escher,SA
AU  - Kooner,JS
AU  - McCarthy,MI
AU  - Palmer,CN
AU  - Wellcome,Trust Case Control Consortium
AU  - Hamsten,A
AU  - Caulfield,MJ
AU  - Frayling,TM
AU  - Tobin,MD
AU  - Jarvelin,MR
AU  - Zeggini,E
AU  - Gieger,C
AU  - Chambers,JC
AU  - Wareham,NJ
AU  - Munroe,PB
AU  - Franks,PW
AU  - Samani,NJ
AU  - Deloukas,P
DO  - hmg/ddw227
EP  - 4106
PY  - 2016///
SN  - 1460-2083
SP  - 4094
TI  - Analysis with the exome array identifies multiple new independent variants in lipid loci.
T2  - Human Molecular Genetics
UR  - http://dx.doi.org/10.1093/hmg/ddw227
UR  - http://hdl.handle.net/10044/1/40217
VL  - 25
ER  -

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