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Nat Commun. 2019 Jan 22;10(1):376. doi: 10.1038/s41467-018-08008-w.

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Kilpeläinen TO1,2, Bentley AR3, Noordam R4, Sung YJ5, Schwander K5, Winkler TW6, Jakupović H7, Chasman DI8,9, Manning A10,11, Ntalla I12, Aschard H13,14, Brown MR15, de Las Fuentes L5,16, Franceschini N17, Guo X18, Vojinovic D19, Aslibekyan S20, Feitosa MF21, Kho M22, Musani SK23, Richard M24, Wang H25, Wang Z15, Bartz TM26, Bielak LF22, Campbell A27, Dorajoo R28, Fisher V29, Hartwig FP30,31, Horimoto ARVR32, Li C33, Lohman KK34, Marten J35, Sim X36, Smith AV37,38, Tajuddin SM39, Alver M40, Amini M41, Boissel M42, Chai JF36, Chen X43, Divers J44, Evangelou E45,46, Gao C47, Graff M17, Harris SE27,48, He M49, Hsu FC44, Jackson AU50, Zhao JH51, Kraja AT21, Kühnel B52,53, Laguzzi F54, Lyytikäinen LP55,56, Nolte IM41, Rauramaa R57, Riaz M58, Robino A59, Rueedi R60,61, Stringham HM50, Takeuchi F62, van der Most PJ41, Varga TV63, Verweij N64, Ware EB65, Wen W66, Li X67, Yanek LR68, Amin N19, Arnett DK69, Boerwinkle E15,70, Brumat M71, Cade B25, Canouil M42, Chen YI18, Concas MP59, Connell J72, de Mutsert R73, de Silva HJ74, de Vries PS15, Demirkan A19, Ding J75, Eaton CB76, Faul JD65, Friedlander Y77, Gabriel KP78, Ghanbari M19,79, Giulianini F8, Gu CC5, Gu D80, Harris TB81, He J82,83, Heikkinen S84,85, Heng CK86,87, Hunt SC88,89, Ikram MA19,90, Jonas JB91,92, Koh WP36,93, Komulainen P57, Krieger JE32, Kritchevsky SB75, Kutalik Z61,94, Kuusisto J85, Langefeld CD44, Langenberg C51, Launer LJ81, Leander K54, Lemaitre RN95, Lewis CE96, Liang J67; Lifelines Cohort Study, Liu J28,97, Mägi R40, Manichaikul A98, Meitinger T99,100, Metspalu A40, Milaneschi Y101, Mohlke KL102, Mosley TH Jr103, Murray AD104, Nalls MA105,106, Nang EK36, Nelson CP107,108, Nona S109, Norris JM110, Nwuba CV7, O'Connell J111,112, Palmer ND113, Papanicolau GJ114, Pazoki R45, Pedersen NL43, Peters A53,115, Peyser PA22, Polasek O116,117,118, Porteous DJ27,48, Poveda A63, Raitakari OT119,120, Rich SS98, Risch N121, Robinson JG122, Rose LM8, Rudan I123, Schreiner PJ124, Scott RA51, Sidney SS125, Sims M23, Smith JA22,65, Snieder H41, Sofer T11,25, Starr JM48,126, Sternfeld B125, Strauch K127,128, Tang H129, Taylor KD18, Tsai MY130, Tuomilehto J131,132, Uitterlinden AG133, van der Ende MY64, van Heemst D4, Voortman T19, Waldenberger M52,53, Wennberg P134, Wilson G135, Xiang YB136, Yao J18, Yu C49, Yuan JM137,138, Zhao W22, Zonderman AB139, Becker DM68, Boehnke M50, Bowden DW113, de Faire U54, Deary IJ48,140, Elliott P45,141, Esko T40,142, Freedman BI143, Froguel P42,144, Gasparini P59,71, Gieger C52,145, Kato N62, Laakso M85, Lakka TA57,84,146, Lehtimäki T55,56, Magnusson PKE43, Oldehinkel AJ147, Penninx BWJH101, Samani NJ107,108, Shu XO66, van der Harst P64,148,149, Van Vliet-Ostaptchouk JV150, Vollenweider P151, Wagenknecht LE152, Wang YX92, Wareham NJ51, Weir DR65, Wu T49, Zheng W66, Zhu X67, Evans MK39, Franks PW63,134,153,154, Gudnason V37,155, Hayward C35, Horta BL30, Kelly TN82, Liu Y156, North KE17, Pereira AC32, Ridker PM8,9, Tai ES36,93,157, van Dam RM36,157, Fox ER158, Kardia SLR22, Liu CT29, Mook-Kanamori DO73,159, Province MA21, Redline S25, van Duijn CM19, Rotter JI18, Kooperberg CB160, Gauderman WJ161, Psaty BM125,162, Rice K163, Munroe PB12,164, Fornage M24, Cupples LA29,165, Rotimi CN3, Morrison AC15, Rao DC166, Loos RJF167,168.

Author information

1
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark. tuomas.kilpelainen@sund.ku.dk.
2
Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA. tuomas.kilpelainen@sund.ku.dk.
3
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, USA.
4
Internal Medicine, Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
5
Division of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA.
6
Department of Genetic Epidemiology, University of Regensburg, Regensburg, 93051, Germany.
7
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
8
Preventive Medicine, Brigham and Women's Hospital, Boston, 02215, MA, USA.
9
Harvard Medical School, Boston, 02131, MA, USA.
10
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, 02114, MA, USA.
11
Department of Medicine, Harvard Medical School, Boston, 02115, MA, USA.
12
Clinical Pharmacology, William Harvey Research Instititute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
13
Department of Epidemiology, Harvard School of Public Health, Boston, 02115, MA, USA.
14
Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, 75015, France.
15
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, 77030, TX, USA.
16
Cardiovascular Division, Department of Medicine, Washington University, St. Louis, 63110, MO, USA.
17
Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, 27514, NC, USA.
18
The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, 90502, CA, USA.
19
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
20
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, 35294, AL, USA.
21
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, 63108, MO, USA.
22
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, USA.
23
Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, 39213, MS, USA.
24
Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
25
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, 02115, MA, USA.
26
Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, 98101, WA, USA.
27
Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
28
Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, 138672, Singapore.
29
Biostatistics, Boston University School of Public Health, Boston, 02118, MA, USA.
30
Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, 96020220, RS, Brazil.
31
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, UK.
32
Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, 01246903, SP, Brazil.
33
Epidemiology and Biostatistics, University of Giorgia at Athens College of Public Health, Athens, 30602, GA, USA.
34
Public Health Sciences, Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, 27157, NC, USA.
35
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
36
Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
37
Icelandic Heart Association, 201, Kopavogur, Iceland.
38
Department of Biostatistics, University of Michigan, Ann Arbor, 48109, MI, USA.
39
Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, 21224, MD, USA.
40
Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
41
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
42
CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, 59000, France.
43
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, 17177, Sweden.
44
Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
45
Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
46
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
47
Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
48
Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
49
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, 430014, China.
50
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
51
MRC Epidemiology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK.
52
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
53
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
54
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17177, Sweden.
55
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33014, Finland.
56
Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
57
Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
58
College of Medicine, Biological Sciences and Psychology, Health Sciences, The Infant Mortality and Morbidity Studies (TIMMS), Leicester, LE1 7RH, UK.
59
Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
60
Department of Computational Biology, University of Lausanne, Lausanne, 1015, Switzerland.
61
Swiss Institute of Bioinformatics, 1015, Lausanne, Switzerland.
62
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 1628655, Japan.
63
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, 20502, Sweden.
64
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, 9700 RB, The Netherlands.
65
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, 48104, MI, USA.
66
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, 37203, TN, USA.
67
Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, 44106, OH, USA.
68
Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
69
Dean's Office, University of Kentucky College of Public Health, Lexington, 40536, KY, USA.
70
Human Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, TX, USA.
71
Department of Medical Sciences, University of Trieste, Trieste, 34137, Italy.
72
Ninewells Hospital & Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK.
73
Clinical Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, Netherlands.
74
Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, 11600, Sri Lanka.
75
Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
76
Department of Family Medicine and Epidemiology, Alpert Medical School of Brown University, Providence, 02860, RI, USA.
77
Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, 91120, Israel.
78
Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Austin, Austin, 78712, TX, USA.
79
Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, 91778-99191, Iran.
80
Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100006, China.
81
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, 20892, MD, USA.
82
Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, 70112, LA, USA.
83
Medicine, Tulane University School of Medicine, New Orleans, 70112, LA, USA.
84
Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, 70211, Finland.
85
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 70210, Finland.
86
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
87
Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, 119228, Singapore.
88
Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, 84132, UT, USA.
89
Department of Genetic Medicine, Weill Cornell Medicine, Doha, 24144, Qatar.
90
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, 3015 GD, The Netherlands.
91
Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim, 68167, Germany.
92
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
93
Health Services and Systems Research, Duke-NUS Medical School, Singapore, 169857, Singapore.
94
Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, 1010, Switzerland.
95
Cardiovascular Health Research Unit, Medicine, University of Washington, Seattle, 98101, WA, USA.
96
Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, School of Medicine, Birmingham, 35294, AL, USA.
97
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
98
Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, 22908, VA, USA.
99
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
100
Institute of Human Genetics, Technische Universität München, Munich, 80333, Germany.
101
Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, 1081 HV, The Netherlands.
102
Department of Genetics, University of North Carolina, Chapel Hill, 27514, NC, USA.
103
Geriatrics, Medicine, University of Mississippi, Jackson, 39216, MS, USA.
104
The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
105
Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, 20892, MD, USA.
106
Data Tecnica International, Glen Echo, 20812, MD, USA.
107
Department of Cardiovascular Sciences, University of Leicester, Leicester, LE3 9PQ, UK.
108
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QD, UK.
109
Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, Seattle, 98101, WA, USA.
110
Department of Epidemiology, University of Colorado Denver, Aurora, 80045, CO, USA.
111
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, 21201, MD, USA.
112
Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, 21201, MD, USA.
113
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
114
Epidemiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, 20892, MD, USA.
115
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Neuherberg, 85764, Germany.
116
Department of Public Health, Department of Medicine, University of Split, Split, 21000, Croatia.
117
Psychiatric Hospital "Sveti Ivan", Zagreb, 10000, Croatia.
118
Gen-Info Ltd., 10000, Zagreb, Croatia.
119
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20521, Finland.
120
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland.
121
Institute for Human Genetics, Department of Epidemiology and Biostatistics, University of California, San Francisco, 94143, CA, USA.
122
Department of Epidemiology and Medicine, University of Iowa, Iowa City, 52242, IA, USA.
123
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK.
124
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, 55454, MN, USA.
125
Kaiser Permanente Washington, Health Research Institute, Seattle, 98101, WA, USA.
126
Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
127
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
128
Institute of Medical Informatics Biometry and Epidemiology, Ludwig-Maximilians-Universitat Munchen, Munich, 81377, Germany.
129
Department of Genetics, Stanford University, Stanford, 94305, CA, USA.
130
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, 55455, MN, USA.
131
Public Health Solutions, National Institute for Health and Welfare, Helsinki, 00271, Finland.
132
Diabetes Research Group, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
133
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 CE, The Netherlands.
134
Department of Public Health & Clinical Medicine, Umeå University, Umeå, 90185, Västerbotten, Sweden.
135
Jackson Heart Study, School of Public Health, Jackson State University, Jackson, 39213, MS, USA.
136
State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200000, China.
137
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, 15261, PA, USA.
138
Division of Cancer Control and Population Sciences, UPMC Hillman Cancer, University of Pittsburgh, Pittsburgh, 15232, PA, USA.
139
Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, 21224, MD, USA.
140
Psychology, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
141
MRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG, UK.
142
Broad Institute of the Massachusetts Institute of Technology and Harvard University, Boston, 02142, MA, USA.
143
Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
144
Department of Genomics of Common Disease, Imperial College London, London, W12 0NN, UK.
145
German Center for Diabetes Research (DZD e.V.), Neuherberg, 85764, Germany.
146
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, 70210, Finland.
147
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
148
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands.
149
Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, 1105 AZ, The Netherlands.
150
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
151
Internal Medicine, Department of Medicine, Lausanne University Hospital, Lausanne, 1011, Switzerland.
152
Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
153
Harvard T. H. Chan School of Public Health, Department of Nutrition, Harvard University, Boston, 02115, MA, USA.
154
OCDEM, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 7LE, UK.
155
Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
156
Public Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, Winston-Salem, 27157, NC, USA.
157
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
158
Cardiology, Medicine, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
159
Public Health and Primary Care, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
160
Fred Hutchinson Cancer Research Center, University of Washington School of Public Health, Seattle, 98109, WA, USA.
161
Biostatistics, Preventive Medicine, University of Southern California, Los Angeles, 90032, CA, USA.
162
Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, Seattle, 98101, WA, USA.
163
Department of Biostatistics, University of Washington, Seattle, 98105, WA, USA.
164
NIHR Barts Cardiovascular Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
165
NHLBI Framingham Heart Study, Framingham, 01702, MA, USA.
166
Division of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA. rao@wustl.edu.
167
Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, 10029, NY, USA. ruth.loos@mssm.edu.
168
Icahn School of Medicine at Mount Sinai, The Mindich Child Health and Development Institute, New York, 10029, NY, USA. ruth.loos@mssm.edu.

Abstract

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

PMID:
30670697
PMCID:
PMC6342931
DOI:
10.1038/s41467-018-08008-w
[Indexed for MEDLINE]
Free PMC Article

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