A pleiotropic QTL on 2p influences serum Lp-PLA2 activity and LDL cholesterol concentration in a baboon model for the genetics of atherosclerosis risk factors

Amanda Vinson, M. C. Mahaney, L. A. Cox, J. Rogers, J. L. VandeBerg, D. L. Rainwater

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2), the major portion of which is bound to low-density lipoprotein, is an independent biomarker of cardiovascular disease risk. To search for common genetic determinants of variation in both Lp-PLA2 activity and LDL cholesterol (LDL-C) concentration, we assayed these substances in serum from 679 pedigreed baboons. Using a maximum likelihood-based variance components approach, we detected significant evidence for a QTL affecting Lp-PLA2 activity (LOD = 2.79, genome-wide P = 0.039) and suggestive evidence for a QTL affecting LDL-C levels (LOD = 2.16) at the same location on the baboon ortholog of human chromosome 2p. Because we also found a significant genetic correlation between the two traits (ρG = 0.50, P <0.00001), we conducted bivariate linkage analyses of Lp-PLA2 activity and LDL-C concentration. These bivariate analyses improved the evidence (LOD = 3.19, genome-wide P = 0.015) for a QTL at the same location on 2p, corresponding to the human cytogenetic region 2p24.3-p23.2. The QTL-specific correlation between the traits (ρQ = 0.62) was significantly different from both zero and 1 (P[ρQ = 0] = 0.047; P[ρQ = 1] = 0.022), rejecting the hypothesis of co-incident linkage and consistent with incomplete pleiotropy at this locus. We conclude that polymorphisms at the QTL described in this study exert some genetic effects that are shared between Lp-PLA2 activity and LDL-C concentration.

Original languageEnglish (US)
Pages (from-to)667-673
Number of pages7
JournalAtherosclerosis
Volume196
Issue number2
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

1-Alkyl-2-acetylglycerophosphocholine Esterase
Papio
Genetic Models
LDL Cholesterol
Atherosclerosis
Serum
Genome
Human Chromosomes
LDL Lipoproteins
Cytogenetics
Cardiovascular Diseases
Biomarkers

Keywords

  • Baboon
  • Bivariate
  • Genome scan
  • LDL cholesterol
  • Lp-PLA
  • Pleiotropy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A pleiotropic QTL on 2p influences serum Lp-PLA2 activity and LDL cholesterol concentration in a baboon model for the genetics of atherosclerosis risk factors. / Vinson, Amanda; Mahaney, M. C.; Cox, L. A.; Rogers, J.; VandeBerg, J. L.; Rainwater, D. L.

In: Atherosclerosis, Vol. 196, No. 2, 02.2008, p. 667-673.

Research output: Contribution to journalArticle

Vinson, Amanda ; Mahaney, M. C. ; Cox, L. A. ; Rogers, J. ; VandeBerg, J. L. ; Rainwater, D. L. / A pleiotropic QTL on 2p influences serum Lp-PLA2 activity and LDL cholesterol concentration in a baboon model for the genetics of atherosclerosis risk factors. In: Atherosclerosis. 2008 ; Vol. 196, No. 2. pp. 667-673.
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AB - Lipoprotein-associated phospholipase A2 (Lp-PLA2), the major portion of which is bound to low-density lipoprotein, is an independent biomarker of cardiovascular disease risk. To search for common genetic determinants of variation in both Lp-PLA2 activity and LDL cholesterol (LDL-C) concentration, we assayed these substances in serum from 679 pedigreed baboons. Using a maximum likelihood-based variance components approach, we detected significant evidence for a QTL affecting Lp-PLA2 activity (LOD = 2.79, genome-wide P = 0.039) and suggestive evidence for a QTL affecting LDL-C levels (LOD = 2.16) at the same location on the baboon ortholog of human chromosome 2p. Because we also found a significant genetic correlation between the two traits (ρG = 0.50, P <0.00001), we conducted bivariate linkage analyses of Lp-PLA2 activity and LDL-C concentration. These bivariate analyses improved the evidence (LOD = 3.19, genome-wide P = 0.015) for a QTL at the same location on 2p, corresponding to the human cytogenetic region 2p24.3-p23.2. The QTL-specific correlation between the traits (ρQ = 0.62) was significantly different from both zero and 1 (P[ρQ = 0] = 0.047; P[ρQ = 1] = 0.022), rejecting the hypothesis of co-incident linkage and consistent with incomplete pleiotropy at this locus. We conclude that polymorphisms at the QTL described in this study exert some genetic effects that are shared between Lp-PLA2 activity and LDL-C concentration.

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