Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration[S]
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-centri...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520355073 |
| id |
doaj-819c0e922beb433098b5dd8420890c6e |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration[S] Journal of Lipid Research high density lipoprotein genetics vascular biology exocyst complex component 3-like 1 |
| author_facet |
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 |
| author_sort |
Matthew B. Lanktree |
| title |
Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration[S] |
| title_short |
Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration[S] |
| title_full |
Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration[S] |
| title_fullStr |
Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration[S] |
| title_full_unstemmed |
Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration[S] |
| title_sort |
genetic meta-analysis of 15,901 african americans identifies variation in exoc3l1 is associated with hdl concentration[s] |
| publisher |
Elsevier |
| series |
Journal of Lipid Research |
| issn |
0022-2275 |
| publishDate |
2015-09-01 |
| description |
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. |
| topic |
high density lipoprotein genetics vascular biology exocyst complex component 3-like 1 |
| url |
http://www.sciencedirect.com/science/article/pii/S0022227520355073 |
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doaj-819c0e922beb433098b5dd8420890c6e2021-04-28T06:00:02ZengElsevierJournal of Lipid Research0022-22752015-09-0156917811786Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration[S]Matthew B. Lanktree0Clara C. Elbers1Yun Li2Guosheng Zhang3Qing Duan4Konrad J. Karczewski5Yiran Guo6Vinicius Tragante7Kari E. North8Mary Cushman9Folkert W. Asselbergs10James G. Wilson11Leslie A. Lange12Fotios Drenos13Alex P. Reiner14Michael R. Barnes15Brendan J. Keating16To whom correspondence should be addressed. (M.B.L.); (B.J.K.); Department of Medicine, McMaster University, Hamilton, Ontario, Canada; To whom correspondence should be addressed. (M.B.L.); (B.J.K.)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 NetherlandsDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NCDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NCDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NCAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MACenter for Applied Genomics, Abramson Research Center, Children's Hospital of Philadelphia, Philadelphia, PADepartment 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 NetherlandsDepartment of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NCDepartments of Medicine and Pathology,University of Vermont, Colchester, VTDepartment 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 NetherlandsDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MSDepartment of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NCCentre for Cardiovascular Genetics, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United KindomDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WAWilliam Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United KindomTo whom correspondence should be addressed. (M.B.L.); (B.J.K.); Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Transplantation, Department of Surgery, University of Pennsylvania, Philadelphia, PA; To whom correspondence should be addressed. (M.B.L.); (B.J.K.)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.http://www.sciencedirect.com/science/article/pii/S0022227520355073high density lipoproteingeneticsvascular biologyexocyst complex component 3-like 1 |