TY - JOUR
T1 - Pleiotropic QTL on chromosome 12q23-q24 influences triglyceride and high-density lipoprotein cholesterol levels
T2 - The HERITAGE family study
AU - Feitosa, Mary F.
AU - Rice, Treva
AU - Borecki, Ingrid B.
AU - Rankinen, Tuomo
AU - Leon, Arthur S.
AU - Skinner, James S.
AU - Després, Jean Pierre
AU - Blangero, John
AU - Bouchard, Claude
AU - Rao, D. C.
PY - 2006/6
Y1 - 2006/6
N2 - 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 IGFI 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 IGFI or another nearby gene is responsible for the concomitant variation in TG and HDL-C levels.
AB - 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 IGFI 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 IGFI or another nearby gene is responsible for the concomitant variation in TG and HDL-C levels.
KW - Bivariate linkage analysis
KW - Coronary heart disease
KW - High-density lipoprotein (HDL)
KW - Insulin-like growth factor 1 (IGF1)
KW - Lipid
KW - Lipoprotein
KW - Quantitative trait loci
KW - Triglycerides
UR - http://www.scopus.com/inward/record.url?scp=33845569867&partnerID=8YFLogxK
U2 - 10.1353/hub.2006.0043
DO - 10.1353/hub.2006.0043
M3 - Article
C2 - 17216804
AN - SCOPUS:33845569867
SN - 0018-7143
VL - 78
SP - 317
EP - 327
JO - Human Biology
JF - Human Biology
IS - 3
ER -