A genome scan for loci influencing levels and trends of lipoprotein lipid-related traits since childhood: The Bogalusa Heart Study.
Coronary heart disease is the result of life-long processes. Previous genetic linkage analyses of lipid and lipoprotein variables that can be measured throughout life have focused on a single measure at one point in time. Genome-wide linkage analyses were performed in the present study to identify loci influencing the long-term levels and trends of high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC) and triglycerides in a longitudinal cohort. Microsatellite markers (n=357) were typed on 779 white and 444 black siblings, ages 14-43 years. Subjects had been examined serially 2-13 times with 6963 serial observations over an average of 22 years from childhood to adulthood. Total and incremental area under the growth curves of lipid traits was calculated and used as measures for long-term levels and trends. After adjusting for age, sex and body mass index, heritability estimates of total area values for all lipid variables were higher than those of a single measurement in either childhood or adulthood. In blacks, significant linkage to LDLC incremental area (peak LOD=3.6 at 50 cM) was observed on chromosome 1; and suggestive linkage for total area of LDLC (LOD=2.9 at 21 cM) on chromosome 19. Only one suggestive linkage (LOD=2.2 at 161 cM) on chromosome 2 was identified in whites for LDLC incremental area. Other suggestive linkage (LOD> or =2.0) was noted for LDLC and HDLC in terms of either total or incremental area on chromosomes 2, 5, 7 and 15 for blacks and whites. Several lipid-related candidate genes such as low-density lipoprotein receptor (LDLR), LDL receptor-related proteins 3 and 8, ApoE, ApoAII and ApoCII are located in these regions. Linkage evidence found in this community-based study indicates that regions on these chromosomes harbor genetic loci that affect the propensity to develop dyslipidemia from childhood.
Chen
Wei
W
Tulane Center for Cardiovascular Health, Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA.
Li
Shengxu
S
Srinivasan
Sathanur R
SR
Boerwinkle
Eric
E
Berenson
Gerald S
GS