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

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 < 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.

• Authors: Sekar Kathiresan, Olle Melander, Candace Guiducci, Aarti Surti, Noël P Burtt, Mark J Rieder, Gregory M Cooper, Charlotta Roos, Benjamin F Voight, Aki S Havulinna, Björn Wahlstrand, Thomas Hedner, Dolores Corella, E Shyong Tai, Jose M Ordovas, Göran Berglund, Erkki Vartiainen, Pekka Jousilahti, Bo Hedblad, Marja-Riitta Taskinen, Christopher Newton-Cheh, Veikko Salomaa, Leena Peltonen, Leif Groop, David M Altshuler, Marju Orho-Melander
• Journal: Nature genetics (Nat Genet) Vol. 40 Issue 2 Pg. 189-97 (Feb 2008) ISSN: 1546-1718 [Electronic] United States
• PMID: 18193044 (Publication Type: Comparative Study, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, HDL
• Cholesterol, LDL
• Genetic Markers
• RNA, Messenger
• Triglycerides

Topics

• Aged
• Alleles
• Case-Control Studies
• Cholesterol, HDL (blood, genetics)
• Cholesterol, LDL (blood, genetics)
• Chromosomes, Human, Pair 1
• Chromosomes, Human, Pair 19
• Chromosomes, Human, Pair 7
• Chromosomes, Human, Pair 8
• Cohort Studies
• Female
• Gene Frequency
• Genetic Markers
• Genetic Variation
• Genome, Human
• Humans
• Linkage Disequilibrium
• Liver (metabolism)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Probability
• Prospective Studies
• RNA, Messenger (metabolism)
• Randomized Controlled Trials as Topic
• Sequence Analysis, DNA
• Triglycerides (blood, genetics)