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Nat Genet. 2017 Jan;49(1):125-130. doi: 10.1038/ng.3738. Epub 2016 Dec 5.

Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.

Author information

1
NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA.
2
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
3
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
4
Wellcome Trust Center for Human Genetics, University of Oxford, Oxford, UK.
5
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
6
Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
7
Department of Genetics, Washington University, St. Louis, Missouri, USA.
8
Division of Epidemiology and Biostatistics, Department of Population and Public Health Sciences, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA.
9
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
10
South Texas Diabetes and Obesity Institute, University of Texas Health Science Center at San Antonio &University of Texas of the Rio Grande Valley, Brownsville, Texas, USA.
11
Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.
12
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
13
German Center for Cardiovascular Research (DZHK), Greifswald, Germany.
14
TOPS Nutrition and Obesity Research Center, Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, USA.
15
University of Maryland School of Medicine, Baltimore, Maryland, USA.
16
Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
17
Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
18
Icelandic Heart Association, Kopavogur, Iceland.
19
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
20
TOPS Obesity and Metabolic Research Center, Biotechnology and Bioengineering Center, Department of Physiology at the Medical College of Wisconsin, Wisconsin, USA.
21
Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden.
22
Department of Neuroradiology, University Hospital Berne, Berne, Switzerland.
23
National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA.
24
Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
25
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
26
Department of Radiology and Radiologic Sciences, Department of Cardiovascular Medicine and Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
27
Center for Genomics and Personalized Medicine Research, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
28
Department of Biochemistry, Center for Diabetes Research, and Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
29
Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center (UTHealth) School of Public Health Brownsville Campus, Brownsville, Texas, USA.
30
Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
31
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
32
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
33
Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
34
Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA.
35
Department of Biostatistics, University of Liverpool, Liverpool, UK.
36
University of Mississippi Medical Center, Jackson, Mississippi, USA.
37
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
38
German Center for Diabetes Research (DZD), Greifswald, Germany.
39
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
40
Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego School of Medicine, San Diego, California, USA.
41
Li Ka Shing Center for Health Information and Discovery, Big Data Institute, University of Oxford, Oxford, UK.
42
Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
43
Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
44
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
45
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
46
Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
47
Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10-8; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

PMID:
27918534
PMCID:
PMC5451114
DOI:
10.1038/ng.3738
[Indexed for MEDLINE]
Free PMC Article

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