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Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

Kathiresan, Sekar; Melander, Olle LU ; Guiducci, Candace; Surti, Aarti; Burtt, Noel P; Rieder, Mark J; Cooper, Gregory M; Roos, Charlotta LU ; Voight, Benjamin F and Havulinna, Aki S, et al. (2008) In Nature Genetics 40(2). p.189-197
Abstract
Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of... (More)
Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care. (Less)
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publication status
published
subject
in
Nature Genetics
volume
40
issue
2
pages
189 - 197
publisher
Nature Publishing Group
external identifiers
  • pmid:18193044
  • wos:000252732900017
  • scopus:38649132270
ISSN
1546-1718
DOI
10.1038/ng.75
language
English
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yes
id
9a463ad0-cb87-4718-a0e8-320856369f69 (old id 1143930)
date added to LUP
2008-08-15 09:15:29
date last changed
2017-11-19 03:49:16
@article{9a463ad0-cb87-4718-a0e8-320856369f69,
  abstract     = {Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P &lt; 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.},
  author       = {Kathiresan, Sekar and Melander, Olle and Guiducci, Candace and Surti, Aarti and Burtt, Noel P and Rieder, Mark J and Cooper, Gregory M and Roos, Charlotta and Voight, Benjamin F and Havulinna, Aki S and Wahlstrand, Bjorn and Hedner, Thomas and Corella, Dolores and Tai, E Shyong and Ordovas, Jose and Berglund, Göran and Vartiainen, Erkki and Jousilahti, Pekka and Hedblad, Bo and Taskinen, Marja-Riitta and Newton-Cheh, Christopher and Salomaa, Veikko and Peltonen, Leena and Groop, Leif and Altshuler, David M and Orho-Melander, Marju},
  issn         = {1546-1718},
  language     = {eng},
  number       = {2},
  pages        = {189--197},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans},
  url          = {http://dx.doi.org/10.1038/ng.75},
  volume       = {40},
  year         = {2008},
}