Title
Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the general population
Author
Beekman, M.
Heijmans, B.T.
Martin, N.G.
Whitfield, J.B.
Pedersen, N.L.
de Faire, U.
Snieder, H.
Lakenberg, N.
Suchiman, H.E.D.
de Knijff, P.
Frants, R.R.
van Ommen, G.J.B.
Kluft, C.
Vogler, G.P.
Boomsma, D.I.
Slagboom, P.E.
Publication year
2003
Abstract
The genetic basis of cardiovascular disease (CVD) with its complex etiology is still largely elusive. Plasma levels of lipids and apolipoproteins are among the major quantitative risk factors for CVD and are well-established intermediate traits that may be more accessible to genetic dissection than clinical CVD end points. Chromosome 19 harbors multiple genes that have been suggested to play a role in lipid metabolism and previous studies indicated the presence of a quantitative trait locus (QTL) for cholesterol levels in genetic isolates. To establish the relevance of genetic variation at chromosome 19 for plasma levels of lipids and apolipoproteins in the general, out-bred Caucasian population, we performed a linkage study in four independent samples, including adolescent Dutch twins and adult Dutch, Swedish and Australian twins totaling 493 dizygotic twin pairs. The average spacing of short-tandem-repeat markers was 6-8 cM. In the three adult twin samples, we found consistent evidence for linkage of chromosome 19 with LDL cholesterol levels (maximum LOD scores of 4.5, 1.7 and 2.1 in the Dutch, Swedish and Australian sample, respectively); no indication for linkage was observed in the adolescent Dutch twin sample. The QTL effects in the three adult samples were not significantly different and a simultaneous analysis of the samples increased the maximum LOD score to 5.7 at 60 cM pter. Bivariate analyses indicated that the putative LDL-C QTL also contributed to the variance in ApoB levels, consistent with the high genetic correlation between these phenotypes. Our study provides strong evidence for the presence of a QTL on chromosome 19 with a major effect on LDL-C plasma levels in outbred Caucasian populations.
Subject
Health
Cardiovascular risk factors
Linkage
Quantitative trait locus (QTL)
Twin pairs
Apolipoprotein
Lipid
Low density lipoprotein cholesterol
Australia
Cardiovascular risk
Caucasian
Cholesterol blood level
Chromosome 19
Controlled study
Dizygotic twins
Genetic correlation
Genetic linkage
Genetic variability
Lipid blood level
Lipid metabolism
Major clinical study
Netherlands
Phenotype
Population research
Quantitative analysis
Quantitative trait locus
Risk factor
Scoring system
Sweden
Tandem repeat
Adolescent
Adult
Aged
Cardiovascular Diseases
Cholesterol, LDL
Chromosomes, Human, Pair 19
European Continental Ancestry Group
Female
Gene Frequency
Genetic Markers
Genetics, Population
Humans
Linkage (Genetics)
Lod Score
Male
Middle Aged
Phenotype
Quantitative Trait Loci
Twins, Dizygotic
Variation (Genetics)
To reference this document use:
http://resolver.tudelft.nl/uuid:d9e65261-2ba7-4617-a99f-4508a08da489
DOI
https://doi.org/10.1038/sj.ejhg.5201053
TNO identifier
237336
ISSN
1018-4813
Source
European Journal of Human Genetics, 11 (11), 845-850
Document type
article