Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q.
High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration.
North
Kari E
KE
Department of Epidemiology, University of North Carolina, Bank of America Center, 137 E. Franklin St., Suite 306, Chapel Hill, NC 27514, USA. kari_north@unc.edu
Miller
Michael B
MB
Coon
Hilary
H
Martin
Lisa J
LJ
Peacock
James M
JM
Arnett
Donna
D
Zhang
Binbin
B
Province
Michael
M
Oberman
Albert
A
Blangero
John
J
Almasy
Laura
L
Ellison
R Curtis
RC
Heiss
Gerardo
G
D000368:Aged; D008078:Cholesterol, LDL / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D014280:Triglycerides / Q000235:genetics*
D008078:Cholesterol, LDL; D014280:Triglycerides