Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans

Alka Malhotra, Hilary Coon, Mary F. Feitosa, Wei Dong Li, Kari E. North, R. Arlen Price, Claude Bouchard, Steven Hunt, Johanna K. Wolford, Eric Boerwinkle, John Buse, Ralph DeFronzo, David Ehrmann, Steven C. Elbein, Wilfred Fujimoto, Steven E. Kahn, Craig L. Hanis, Richard A. Mulivor, Jeanne C. Beck, Jill NorrisM. Alan Permutt, Philip Behn, Leslie Raffel, David C. Robbins

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Abstract

Genetic influences on lipid traits have been suggested by numerous studies. In addition to heritability studies, over 50 genome scans have been performed to identify regions of linkage for quantitative lipid levels. Five of these scans have been performed in African Americans (four univariate and one bivariate linkage analysis), but with results that have been largely inconclusive. Linkage analyses are often limited by both sample size and heterogeneity, which may lead to nominal LOD scores or lack of evidence for linkage; the use of meta-analysis to combine linkage results from populations with similar ethnic backgrounds may help overcome some of these limitations. Thus, we performed a meta-analysis using data from four genome scans conducted in African American families to identify chromosomal regions showing evidence of linkage for total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Significant evidence (i.e. P < 0.00042) for linkage was found for LDL on chromosome 1q32.1-q41 (Pweighted = 0.00014 and Punweighted = 0.00007) and 1q41-q44 (Pweighted = 0.00017 and Punweighted = 0.00014). We found suggestive evidence (i.e. P<0.00847) for TG on 16p12.1-q11.2 and for HDL on 4p15.1-p11. We also assessed heterogeneity between studies and found significant evidence for low heterogeneity for both regions on chromosome 1q (P = 0.0300 and P = 0.0279, respectively) for LDL and chromosome 16 (P = 0.0429) for TG. Statistically significant evidence for linkage and low heterogeneity on chromosome 1q therefore suggest that this region may harbor a gene underlying the inheritance of LDL in African Americans.

Original languageEnglish
Pages (from-to)3955-3962
Number of pages8
JournalHuman Molecular Genetics
Volume14
Issue number24
DOIs
Publication statusPublished - 15 Dec 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Malhotra, A., Coon, H., Feitosa, M. F., Li, W. D., North, K. E., Price, R. A., Bouchard, C., Hunt, S., Wolford, J. K., Boerwinkle, E., Buse, J., DeFronzo, R., Ehrmann, D., Elbein, S. C., Fujimoto, W., Kahn, S. E., Hanis, C. L., Mulivor, R. A., Beck, J. C., ... Robbins, D. C. (2005). Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans. Human Molecular Genetics, 14(24), 3955-3962. https://doi.org/10.1093/hmg/ddi419