title: Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration.
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.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Lanktree
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA Complex Genetics Section, Department of Medical Genetics (DBG), University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Clara C
authors.initials: CC
authors.lastname: Elbers
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Qing
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA.
authors.forename: Konrad J
authors.initials: KJ
authors.lastname: Karczewski
authors.affiliation: Center for Applied Genomics, Abramson Research Center, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Department of Medical Genetics, Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Tragante
authors.affiliation: Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.affiliation: Departments of Medicine and Pathology,University of Vermont, Colchester, VT.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS.
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.affiliation: Department of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kindom.
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Reiner
authors.affiliation: William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kindom.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barnes
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA Division of Transplantation, Department of Surgery, University of Pennsylvania, Philadelphia, PA.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
mesh_terms: D001741:Black or African American / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D033921:Vesicular Transport Proteins / Q000235:genetics*; D044465:White People
chemical_list: C490685:EXOC3 protein, human; D008075:Lipoproteins, HDL; D033921:Vesicular Transport Proteins
keywords: exocyst complex component 3-like 1; genetics; high density lipoprotein; vascular biology