title: 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.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. skathiresan@partners.org
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Candace
authors.initials: C
authors.lastname: Guiducci
authors.forename: Aarti
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authors.lastname: Surti
authors.forename: Noël P
authors.initials: NP
authors.lastname: Burtt
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Rieder
authors.forename: Gregory M
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authors.forename: Charlotta
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authors.lastname: Roos
authors.forename: Benjamin F
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authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.forename: Björn
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authors.lastname: Wahlstrand
authors.forename: Thomas
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authors.lastname: Hedner
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Göran
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authors.lastname: Berglund
authors.forename: Erkki
authors.initials: E
authors.lastname: Vartiainen
authors.forename: Pekka
authors.initials: P
authors.lastname: Jousilahti
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: David M
authors.initials: DM
authors.lastname: Altshuler
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood* / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D015810:Linkage Disequilibrium; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood* / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005819:Genetic Markers; D012333:RNA, Messenger; D014280:Triglycerides