Human Molecular Genetics Advance Access originally published online on November 21, 2005
Human Molecular Genetics 2005 14(24):3955-3962; doi:10.1093/hmg/ddi419
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Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans
1Diabetes and Obesity Research Unit, Translational Genomics Research Institute, Phoenix, AZ 85004, USA, 2Psychiatry Department and 3Cardiovascular Genetics Division, University of Utah, Salt Lake City, UT 84108, USA, 4Division of Biostatistics, Washington University, St Louis, MO 63110, USA, 5Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA, 6Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA and 7Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70804, USA
* To whom correspondence should be addressed at: Diabetes and Obesity Research Unit, Genetic Basis of Human Disease, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ 85004, USA. Tel: +1 6023438749; Fax: +1 6023438840; Email: amalhotra{at}tgen.org
Received September 15, 2005; Accepted November 3, 2005
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.
A list of the American Diabetes Association GENNID study group members can be found in the Acknowledgements section.
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