TY - JOUR
T1 - Evidence of QTL on 15q21 for high-density lipoprotein cholesterol
T2 - The National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS)
AU - Feitosa, Mary F.
AU - Province, Michael A.
AU - Heiss, Gerardo
AU - Arnett, Donna K.
AU - Myers, Richard H.
AU - Pankow, James S.
AU - Hopkins, Paul N.
AU - Borecki, Ingrid B.
N1 - Funding Information:
Support was provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL 67893, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, and U01 HL67902. Support was also partially provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, and U01 HL56569. This report is presented on behalf of the investigators of the NHLBI Family Heart Study. The investigators thank the study participants and staff for their valuable contributions.
PY - 2007/1
Y1 - 2007/1
N2 - A genome-wide linkage scan was conducted to identify regions potentially having quantitative trait loci (QTLs) influencing high-density lipoprotein (HDL) cholesterol. We found suggestive evidence of a QTL (lod score (LOD) = 1.75, p = 0.00224, and q = 0.07649) influencing the variation of plasma levels of age- and sex-adjusted HDL-cholesterol on chromosome 15q21 at marker D15S659 in the NHLBI FHS data. Owing to the perturbations to lipid profiles associated with diabetes, the analysis was repeated excluding diabetic subjects from the sample. The lod score increased from 1.75 to 2.71 (p = 0.00021, q = 0.05392) at the same chromosome 15 location, despite the reduction in sample size. This finding indicates that the inclusion of diabetic subjects in the analysis may confound the presence of a QTL for HDL-cholesterol on 15q21. Because of the known effects of important covariates such as metabolic variables and lifestyle habits that may interact with a putative QTL, we also analyzed HDL-cholesterol with a progressive adjustment. When body mass index, smoking, and habitual alcohol intake were added to age- and sex-adjustment, we found strong evidence for linkage in the complete sample (LOD = 4.77, p = 0.0000013, and q = 0.00016) as well as in the non-diabetic sub-sample (LOD = 4.52, p = 0.0000025, and q = 0.00026) on chromosome 15q21 (between D15S659 and D15S195 markers). These results suggest that there are multiple pathways and factors involving genetic and environmental effects influencing HDL-cholesterol levels, and by taking some of these known factors into account, we obtained strong evidence of a QTL influencing HDL-cholesterol levels. While this putative QTL may also have an effect in diabetes, our data suggest a more pronounced role in non-diabetics. A prominent candidate gene residing within the linkage region on 15q21 is hepatic lipase (HL), which has a major role in lipoprotein metabolism.
AB - A genome-wide linkage scan was conducted to identify regions potentially having quantitative trait loci (QTLs) influencing high-density lipoprotein (HDL) cholesterol. We found suggestive evidence of a QTL (lod score (LOD) = 1.75, p = 0.00224, and q = 0.07649) influencing the variation of plasma levels of age- and sex-adjusted HDL-cholesterol on chromosome 15q21 at marker D15S659 in the NHLBI FHS data. Owing to the perturbations to lipid profiles associated with diabetes, the analysis was repeated excluding diabetic subjects from the sample. The lod score increased from 1.75 to 2.71 (p = 0.00021, q = 0.05392) at the same chromosome 15 location, despite the reduction in sample size. This finding indicates that the inclusion of diabetic subjects in the analysis may confound the presence of a QTL for HDL-cholesterol on 15q21. Because of the known effects of important covariates such as metabolic variables and lifestyle habits that may interact with a putative QTL, we also analyzed HDL-cholesterol with a progressive adjustment. When body mass index, smoking, and habitual alcohol intake were added to age- and sex-adjustment, we found strong evidence for linkage in the complete sample (LOD = 4.77, p = 0.0000013, and q = 0.00016) as well as in the non-diabetic sub-sample (LOD = 4.52, p = 0.0000025, and q = 0.00026) on chromosome 15q21 (between D15S659 and D15S195 markers). These results suggest that there are multiple pathways and factors involving genetic and environmental effects influencing HDL-cholesterol levels, and by taking some of these known factors into account, we obtained strong evidence of a QTL influencing HDL-cholesterol levels. While this putative QTL may also have an effect in diabetes, our data suggest a more pronounced role in non-diabetics. A prominent candidate gene residing within the linkage region on 15q21 is hepatic lipase (HL), which has a major role in lipoprotein metabolism.
KW - BMI
KW - Covariate
KW - Diabetes
KW - Genetic epidemiology
KW - HDL
KW - Quantitative trait loci
KW - Triglycerides
UR - http://www.scopus.com/inward/record.url?scp=33845523681&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2006.02.006
DO - 10.1016/j.atherosclerosis.2006.02.006
M3 - Article
C2 - 16529751
AN - SCOPUS:33845523681
SN - 0021-9150
VL - 190
SP - 232
EP - 237
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -