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Am J Epidemiol. 2019 Jun 1;188(6):1033-1054. doi: 10.1093/aje/kwz005.

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

de Vries PS1, Brown MR1, Bentley AR2, Sung YJ3, Winkler TW4, Ntalla I5, Schwander K3, Kraja AT6, Guo X7, Franceschini N8, Cheng CY9,10,11, Sim X12, Vojinovic D13, Huffman JE14, Musani SK15, Li C16, Feitosa MF6, Richard MA17, Noordam R18, Aschard H19,20, Bartz TM21, Bielak LF22, Deng X23, Dorajoo R24, Lohman KK25, Manning AK26,27, Rankinen T28, Smith AV29,30, Tajuddin SM31, Evangelou E32,33, Graff M8, Alver M34, Boissel M35, Chai JF12, Chen X36, Divers J37, Gandin I38, Gao C39, Goel A40,41, Hagemeijer Y42, Harris SE43,44, Hartwig FP45,46, He M47, Horimoto ARVR48, Hsu FC37, Jackson AU49, Kasturiratne A50, Komulainen P51, Kühnel B52,53, Laguzzi F54, Lee JH55, Luan J56, Lyytikäinen LP57,58, Matoba N59, Nolte IM60, Pietzner M61,62, Riaz M63,64, Said MA42, Scott RA56, Sofer T27,65, Stančáková A66, Takeuchi F67, Tayo BO68, van der Most PJ60, Varga TV69, Wang Y70, Ware EB71, Wen W72, Yanek LR73, Zhang W32,74, Zhao JH56, Afaq S32, Amin N13, Amini M60, Arking DE75, Aung T9,11,76, Ballantyne C77,78, Boerwinkle E79,80, Broeckel U81, Campbell A82, Canouil M35, Charumathi S9,10, Chen YI7, Connell JM83, de Faire U54, de Las Fuentes L3,84, de Mutsert R85, de Silva HJ86, Ding J87, Dominiczak AF88, Duan Q89, Eaton CB90, Eppinga RN42, Faul JD71, Fisher V23, Forrester T91, Franco OH13,92, Friedlander Y93, Ghanbari M13,94, Giulianini F, Grabe HJ95, Grove ML1, Gu CC3, Harris TB96, Heikkinen S66,97, Heng CK98,99, Hirata M100, Hixson JE79, Howard BV101,102, Ikram MA13,103,104; InterAct Consortium, Jacobs DR105, Johnson C106, Jonas JB107,108, Kammerer CM109, Katsuya T110,111, Khor CC24,112, Kilpeläinen TO113,114, Koh WP12,115, Koistinen HA116,117,118, Kolcic I, Kooperberg C119, Krieger JE48, Kritchevsky SB120, Kubo M121, Kuusisto J66, Lakka TA51,97,122, Langefeld CD37, Langenberg C56, Launer LJ96, Lehne B32, Lemaitre RN123, Li Y3, Liang J70, Liu J24,124, Liu K125, Loh M32,126, Louie T127, Mägi R34, Manichaikul AW128, McKenzie CA91, Meitinger T129,130, Metspalu A34, Milaneschi Y131, Milani L34, Mohlke KL89, Mosley TH132, Mukamal KJ133, Nalls MA134,135, Nauck M61,62, Nelson CP63,64, Sotoodehnia N136, O'Connell JR137,138, Palmer ND139, Pazoki R32, Pedersen NL36, Peters A53,62, Peyser PA22, Polasek O140,141,142, Poulter N143, Raffel LJ144, Raitakari OT145,146, Reiner AP119, Rice TK3, Rich SS147, Robino A148, Robinson JG149, Rose LM150, Rudan I151, Schmidt CO152, Schreiner PJ105, Scott WR32,153, Sever P153, Shi Y9, Sidney S154, Sims M15, Smith BH155, Smith JA22,71, Snieder H60, Starr JM43,156, Strauch K157,158, Tan N9,11, Taylor KD7, Teo YY12,24,159,160,161, Tham YC9, Uitterlinden AG13,162, van Heemst D18, Vuckovic D38, Waldenberger M52,53, Wang L6, Wang Y8, Wang Z1, Wei WB163, Williams C6, Wilson G164, Wojczynski MK6, Yao J7, Yu B1, Yu C47, Yuan JM165,166, Zhao W22, Zonderman AB167, Becker DM73, Boehnke M49, Bowden DW139, Chambers JC32,74,168,169,170,171, Deary IJ43,172, Esko T34,173, Farrall M40,41, Franks PW69,174,175,176, Freedman BI177, Froguel P35,178, Gasparini P38,148, Gieger C52,179, Horta BL45, Kamatani Y59, Kato N67, Kooner JS74,153,169,171, Laakso M66, Leander K54, Lehtimäki T57,58; Lifelines Cohort, Groningen, The Netherlands (Lifelines Cohort Study), Magnusson PKE36, Penninx B131, Pereira AC48, Rauramaa R51, Samani NJ63,64, Scott J153, Shu XO72, van der Harst P42,180, Wagenknecht LE181, Wang YX182, Wareham NJ56, Watkins H40,41, Weir DR71, Wickremasinghe AR50, Zheng W72, Elliott P32,170,171,183,184, North KE8,185, Bouchard C28, Evans MK31, Gudnason V29,30, Liu CT23, Liu Y186, Psaty BM187,188, Ridker PM150,189, van Dam RM12,174,124, Kardia SLR22, Zhu X70, Rotimi CN2, Mook-Kanamori DO85,190, Fornage M1,17, Kelly TN191, Fox ER192, Hayward C14, van Duijn CM13, Tai ES12,115,124, Wong TY9,11,76, Liu J193, Rotter JI7, Gauderman WJ194, Province MA6, Munroe PB5,195, Rice K127, Chasman DI150,189, Cupples LA23,196, Rao DC3, Morrison AC1.

Author information

1
Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas.
2
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
3
Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
4
Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
5
Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
6
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri.
7
Genomic Outcomes, Pediatrics, Institute for Translational Genomics and Population Sciences, LA BioMed at Harbor-UCLA Medical Center, Torrance, California.
8
Epidemiology, University of North Carolina Gilling School of Global Public Health, Chapel Hill, North Carolina.
9
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
10
Centre for Quantitative Medicine, Academic Medicine Research Institute, Ophthalmology & Visual Sciences Academic Clinical Program.
11
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
12
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
13
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
14
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
15
Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
16
Epidemiology and Biostatistics, University of Georgia at Athens College of Public Health, Athens, Georgia.
17
Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas.
18
Internal Medicine, Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
19
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
20
Centre de Bioinformatique, Biostatistique et Biologie Intégrative.
21
Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, Washington.
22
Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan.
23
Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
24
Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
25
Public Health Sciences, Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina.
26
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
27
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
28
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
29
Icelandic Heart Association, Kopavogur, Iceland.
30
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
31
Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
32
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
33
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
34
Estonian Genome Center, University of Tartu, Tartu, Estonia.
35
CNRS UMR 8199, European Genomic Institute for Diabetes.
36
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, Sweden.
37
Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
38
Department of Medical Sciences, University of Trieste, Trieste, Italy.
39
Molecular Genetics and Genomics Program, Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, North Carolina.
40
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom.
41
Wellcome Centre for Human Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom.
42
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
43
Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
44
Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom.
45
Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, RS, Brazil.
46
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
47
Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
48
Laboratory of Genetics and Molecular Cardiology, Heart Institute.
49
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan.
50
Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
51
Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
52
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
53
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
54
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
55
Sergievsky Center and Taub Institute, Columbia University Medical Center, New York, New York.
56
MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
57
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
58
Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
59
Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
60
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
61
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
62
DZHK.
63
Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
64
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.
65
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
66
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
67
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
68
Department of Public Health Sciences, Loyola University Chicago, Maywood, Illinois.
69
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
70
Department of Population and Quantitative Health and Sciences, Case Western Reserve University, Cleveland, Ohio.
71
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
72
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
73
Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
74
Department of Cardiology, Ealing Hospital, Middlesex, United Kingdom.
75
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
76
Ophthalmology & Visual Sciences Academic Clinical Program.
77
Section of Cardiovascular Research, Baylor College of Medicine, Houston, Texas.
78
Houston Methodist Debakey Heart and Vascular Center, Houston, Texas.
79
Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas.
80
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
81
Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
82
Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
83
Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, United Kingdom.
84
Cardiovascular Division, Department of Medicine, Washington University, St. Louis, Missouri.
85
Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
86
Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
87
Center on Diabetes, Obesity, and Metabolism, Gerontology and Geriatric Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina.
88
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
89
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina.
90
Department of Family Medicine and Epidemiology, Alpert Medical School of Brown University, Providence, Rhode Island.
91
Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Jamaica.
92
Institute of Social and Preventive Medicine.
93
Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
94
Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
95
Department Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
96
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
97
Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Finland.
98
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
99
Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore, Singapore.
100
Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Japan.
101
MedStar Health Research Institute, Hyattsville, Maryland.
102
Center for Clinical and Translational Sciences and Department of Medicine, Georgetown-Howard Universities, Washington, District of Columbia.
103
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
104
Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
105
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
106
Collaborative Health Studies Coordinating Center, University of Washington, Seattle, Washington.
107
Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
108
Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Capital Medical University, Beijing, China.
109
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
110
Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan.
111
Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
112
Department of Biochemistry, National University of Singapore, Singapore, Singapore.
113
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
114
Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, New York.
115
Duke-NUS Medical School, Singapore, Singapore.
116
Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
117
Department of Medicine and Abdominal Center, Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
118
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
119
Fred Hutchinson Cancer Research Center, University of Washington School of Public Health, Seattle, Washington.
120
Sticht Center for Health Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
121
Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
122
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
123
Cardiovascular Health Research Unit, Medicine, University of Washington, Seattle, Washington.
124
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
125
Epidemiology, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
126
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore.
127
Department of Biostatistics, University of Washington, Seattle, Washington.
128
Biostatistics Section, Center for Public Health Genomics, University of Virginia, School of Medicine, West Complex, Charlottesville, Virginia.
129
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
130
Institute of Human Genetics, Technische Universität München, Munich, Germany.
131
Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, The Netherlands.
132
Geriatrics, Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
133
General Medicine & Primary Care, Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
134
Data Tecnica International, Glen Echo, Maryland.
135
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
136
Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, Washington.
137
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland.
138
Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
139
Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina.
140
Department of Public Health, Department of Medicine, University of Split, Split, Croatia.
141
Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia.
142
Gen-info Ltd, Zagreb, Croatia.
143
School of Public Health, Imperial College London, London, United Kingdom.
144
Division of Genetic and Genomic Medicine, Department of Pediatrics, University of California, Irvine, California.
145
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
146
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
147
Center for Public Health Genomics, University of Virginia, School of Medicine, West Complex, Charlottesville, Virginia.
148
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
149
Department of Epidemiology and Medicine, University of Iowa, Iowa City, Iowa.
150
Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
151
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom.
152
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
153
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
154
Division of Research, Kaiser Permanente of Northern California, Oakland, California.
155
Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.
156
Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, United Kingdom.
157
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
158
Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU, Munich, Germany.
159
Life Sciences Institute, National University of Singapore, Singapore, Singapore.
160
NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore.
161
Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore.
162
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
163
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
164
Jackson Heart Study, School of Public Health, Jackson State University, Jackson, Mississippi.
165
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
166
Division of Cancer Control and Population Sciences, UPMC Hillman Cancer, University of Pittsburgh, Pittsburgh, Pennsylvania.
167
Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
168
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
169
Imperial College Healthcare NHS Trust, London, United Kingdom.
170
MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom.
171
NIHR Imperial College Biomedical Research Centre, Imperial College London, London, United Kingdom.
172
Psychology, The University of Edinburgh, Edinburgh, United Kingdom.
173
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Boston, Massachusetts.
174
Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
175
Department of Public Health & Clinical Medicine, Umeå University, Umeå, Västerbotten, Sweden.
176
OCDEM, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
177
Nephrology, Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
178
Department of Genomics of Common Disease, Imperial College London, London, United Kingdom.
179
German Center for Diabetes Research.
180
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
181
Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
182
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
183
Health Data Research UK.
184
UK Dementia Research Institute.
185
Carolina Center of Genome Sciences, University of North Carolina, Chapel Hill, North Carolina.
186
Public Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, Winston-Salem, North Carolina.
187
Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, Seattle, Washington.
188
Kaiser Permanente Washington, Health Research Institute, Seattle, Washington.
189
Harvard Medical School, Boston, Massachusetts.
190
Public Health and Primary Care, Leiden University Medical Center, Leiden, Leiden.
191
Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.
192
Cardiology, Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
193
WHI CCC, Fred Hutchinson Cancer Research Center, Seattle, Washington.
194
Biostatistics, Preventive Medicine, University of Southern California, Los Angeles, California.
195
NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, United Kingdom.
196
NHLBI Framingham Heart Study, Framingham, Massachusetts.

Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

KEYWORDS:

alcohol consumption; cholesterol; gene-environment interactions; gene-lifestyle interactions; genome-wide association studies; lipids; triglycerides

PMID:
30698716
PMCID:
PMC6545280
[Available on 2020-06-01]
DOI:
10.1093/aje/kwz005

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