title: Pleiotropic QTL on chromosome 12q23-q24 influences triglyceride and high-density lipoprotein cholesterol levels: the HERITAGE family study.
abstract: To determine whether a common quantitative trait locus (QTL) influences the variation of fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels, we used a bivariate multipoint linkage analysis with 654 polymorphic markers in 99 white and 101 black families. The phenotypes were investigated under two conditions: at baseline and after a 20-week exercise training intervention. A maximum genome-wide bivariate LOD score of 3.0 (p = 0.00010) was found on chromosome 12q23-q24, located within the IGF1 gene (insulin-like growth factor 1, at 107 cM) for TG and HDL-C at baseline in whites. This bivariate linkage peak is considerably higher than the univariate linkage results at the same chromosome location for either trait (for TG, LOD = 2.07, p = 0.00108; for HDL-C, LOD = 2.04, p = 0.00101). The genetic correlations between baseline TG and HDL-C levels were -0.14 for the residual and -0.33 for the QTL components. Moreover, association analysis showed that TG, HDL-C, and IGF1 are significantly associated (p = 0.04). In conclusion, these results suggest that a QTL on chromosome 12q23-q24 influences the variation of plasma TG and HDL-C levels. Further investigation should confirm whether IGF1 or another nearby gene is responsible for the concomitant variation in TG and HDL-C levels.
authors.affiliation: Division of Statistical Genomics in the Center for Genome Sciences, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Feitosa
authors.forename: Treva
authors.initials: T
authors.lastname: Rice
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Tuomo
authors.initials: T
authors.lastname: Rankinen
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Leon
authors.forename: James S
authors.initials: JS
authors.lastname: Skinner
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.forename: D C
authors.initials: DC
authors.lastname: Rao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D015444:Exercise; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D040641:Quantitative Trait Loci / Q000235:genetics*; D014280:Triglycerides / Q000097:blood / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D005819:Genetic Markers; D014280:Triglycerides