Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration |
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| Authors: | Matthew B Lanktree Clara C Elbers Yun Li Guosheng Zhang Qing Duan Konrad J Karczewski Yiran Guo Vinicius Tragante Kari E North Mary Cushman Folkert W Asselbergs James G Wilson Leslie A Lange Fotios Drenos Alex P Reiner Michael R Barnes Brendan J Keating |
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| Institution: | 2. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA;3. Complex Genetics Section, Department of Medical Genetics (DBG), University Medical Center Utrecht, Utrecht, The Netherlands;11. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands;12. Department of Medical Genetics, Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands;4. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC;8. Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC;6. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA;10. Departments of Medicine and Pathology,University of Vermont, Colchester, VT;112. Department of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC;123. Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kindom;84. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA;106. William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kindom |
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| Abstract: | Meta-analyses of European populations has successfully identified genetic variants in over 150 loci associated with lipid levels, but results from additional ethnicities remain limited. Previously, we reported two novel lipid loci identified in a sample of 7,657 African Americans using a gene-centric array including 50,000 SNPs in 2,100 candidate genes. Initial discovery and follow-up of signals with P < 10?5 in additional African American samples confirmed CD36 and ICAM1. Using an additional 8,244 African American female samples from the Women’s Health Initiative SNP Health Association Resource genome-wide association study dataset, we further examined the previous meta-analyses results by attempting to replicate 20 additional putative lipid signals with P < 10?4. Replication confirmed rs868213, located in a splice donor region of exocyst complex component 3-like 1 (EXOC3L1) as a novel signal for HDL (additive allelic effect β = 0.02; P = 1.4 × 10?8; meta-analyses of discovery and replication). EXOC3L1 is strongly expressed in vascular endothelium and forms part of the exocyst complex, a key facilitator of the trafficking of lipid receptors. Increasing sample sizes for genetic studies in nonEuropean populations will continue to improve our understanding of lipid metabolism. |
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| Keywords: | high density lipoprotein genetics vascular biology exocyst complex component 3-like 1 |
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