Advanced

The impact of low-frequency and rare variants on lipid levels.

Surakka, Ida; Horikoshi, Momoko; Mägi, Reedik; Sarin, Antti-Pekka; Mahajan, Anubha; Lagou, Vasiliki; Marullo, Letizia; Ferreira, Teresa; Miraglio, Benjamin and Timonen, Sanna, et al. (2015) In Nature Genetics 47(6). p.589-597
Abstract
Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol.... (More)
Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
47
issue
6
pages
589 - 597
publisher
Nature Publishing Group
external identifiers
  • wos:000355386500009
  • pmid:25961943
  • scopus:84930090376
ISSN
1546-1718
DOI
10.1038/ng.3300
language
English
LU publication?
yes
id
bbe11594-fa68-4b81-ac3f-fd83165eb4ec (old id 5453441)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25961943?dopt=Abstract
date added to LUP
2015-06-04 18:38:24
date last changed
2017-12-10 03:33:12
@article{bbe11594-fa68-4b81-ac3f-fd83165eb4ec,
  abstract     = {Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.},
  author       = {Surakka, Ida and Horikoshi, Momoko and Mägi, Reedik and Sarin, Antti-Pekka and Mahajan, Anubha and Lagou, Vasiliki and Marullo, Letizia and Ferreira, Teresa and Miraglio, Benjamin and Timonen, Sanna and Kettunen, Johannes and Pirinen, Matti and Karjalainen, Juha and Thorleifsson, Gudmar and Hägg, Sara and Hottenga, Jouke-Jan and Isaacs, Aaron and Ladenvall, Claes and Beekman, Marian and Esko, Tõnu and Ried, Janina S and Nelson, Christopher P and Willenborg, Christina and Gustafsson, Stefan and Westra, Harm-Jan and Blades, Matthew and de Craen, Anton J M and de Geus, Eco J and Deelen, Joris and Grallert, Harald and Hamsten, Anders and Havulinna, Aki S and Hengstenberg, Christian and Houwing-Duistermaat, Jeanine J and Hyppönen, Elina and Karssen, Lennart C and Lehtimäki, Terho and Lyssenko, Valeriya and Magnusson, Patrik K E and Mihailov, Evelin and Müller-Nurasyid, Martina and Mpindi, John-Patrick and Pedersen, Nancy L and Penninx, Brenda W J H and Perola, Markus and Pers, Tune H and Peters, Annette and Rung, Johan and Smit, Johannes H and Steinthorsdottir, Valgerdur and Tobin, Martin D and Tsernikova, Natalia and van Leeuwen, Elisabeth M and Viikari, Jorma S and Willems, Sara M and Willemsen, Gonneke and Schunkert, Heribert and Erdmann, Jeanette and Samani, Nilesh J and Kaprio, Jaakko and Lind, Lars and Gieger, Christian and Metspalu, Andres and Slagboom, P Eline and Groop, Leif and van Duijn, Cornelia M and Eriksson, Johan G and Jula, Antti and Salomaa, Veikko and Boomsma, Dorret I and Power, Christine and Raitakari, Olli T and Ingelsson, Erik and Järvelin, Marjo-Riitta and Thorsteinsdottir, Unnur and Franke, Lude and Ikonen, Elina and Kallioniemi, Olli and Pietiäinen, Vilja and Lindgren, Cecilia M and Stefansson, Kari and Palotie, Aarno and McCarthy, Mark I and Morris, Andrew P and Prokopenko, Inga and Ripatti, Samuli},
  issn         = {1546-1718},
  language     = {eng},
  number       = {6},
  pages        = {589--597},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {The impact of low-frequency and rare variants on lipid levels.},
  url          = {http://dx.doi.org/10.1038/ng.3300},
  volume       = {47},
  year         = {2015},
}