A quantitative trait locus influences coordinated variation in measures of ApoB-containing lipoproteins.
Lipoprotein phenotypes are known to be strongly intercorrelated. These intercorrelations are due to genetic and environmental effects on common metabolic pathways. The purpose of this study was to determine if we could localize genes that exert pleiotropic effects on multiple related lipoprotein traits in humans. Using data from the San Antonio Family Heart Study, we extracted principal components from a set of 12 intercorrelated lipoprotein traits that included phenotypes reflecting lipid and protein concentrations and size distributions for LDLs and HDLs. Five principal components were extracted from the data and all were significantly heritable (h(2) = 0.41-0.57). When subjected to linkage analyses, only one, Component 5, returned a LOD score > or = 3 (LOD score was 3.0 at 38cM on chromosome 15; genome-wide P-value = 0.039). LDL median diameter (-0.529), non-HDLC (-0.422), and ApoB (-0.403) concentrations were the only traits with loadings (absolute value) >0.4, suggesting Component 5 is related to LDL size or perhaps more generally to beta-lipoprotein metabolism. Surprisingly, none of the 12 original lipoprotein traits had a LOD >1 in this region of chromosome 15. These data provide evidence for a novel gene, influencing beta-lipoprotein phenotypes, whose effect(s) is detected only when several lipoprotein traits are considered together.
Rainwater
David L
DL
Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245-0549, USA. david@darwin.sfbr.org
Mahaney
Michael C
MC
VandeBerg
John L
JL
Brush
Gerome
G
Almasy
Laura
L
Blangero
John
J
Dyke
Bennett
B
Hixson
James E
JE
Cole
Shelley A
SA
MacCluer
Jean W
JW
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood* / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008214:Lymphocytes; D008297:Male; D017058:Mexican Americans; D010641:Phenotype; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL