Pleiotropic QTL on chromosome 12q23-q24 influences triglyceride and high-density lipoprotein cholesterol levels: the HERITAGE family study.
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.
Feitosa
Mary E
ME
Division of Statistical Genomics in the Center for Genome Sciences, Washington University School of Medicine, Saint Louis, MO, USA.
Rice
Treva
T
Borecki
Ingrid B
IB
Rankinen
Tuomo
T
Leon
Arthur S
AS
Skinner
James S
JS
Després
Jean-Pierre
JP
Blangero
John
J
Bouchard
Claude
C
Rao
D C
DC
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*
D008076:Cholesterol, HDL; D005819:Genetic Markers; D014280:Triglycerides