title: Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia.
abstract: We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.
authors.affiliation: Department of Medicine (Genetics Program), Boston University School of Medicine, Boston, MA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu
authors.forename: Diego F
authors.initials: DF
authors.lastname: Wyszynski
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Waterworth
authors.forename: Steven D
authors.initials: SD
authors.lastname: Wilton
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Y Antero
authors.initials: YA
authors.lastname: Kesäniemi
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mahley
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Bersot
authors.forename: Qianli
authors.initials: Q
authors.lastname: Ma
authors.forename: Sanjay S
authors.initials: SS
authors.lastname: Sharma
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Montgomery
authors.forename: Lefkos T
authors.initials: LT
authors.lastname: Middleton
authors.forename: Scott S
authors.initials: SS
authors.lastname: Sundseth
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Scott M
authors.initials: SM
authors.lastname: Grundy
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000209:etiology; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D002877:Chromosomes, Human; D050171:Dyslipidemias / Q000150:complications / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D040641:Quantitative Trait Loci / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol