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Nat Genet. 2017 Dec;49(12):1758-1766. doi: 10.1038/ng.3977. Epub 2017 Oct 30.

Exome-wide association study of plasma lipids in >300,000 individuals.

Liu DJ1, Peloso GM2,3, Yu H4, Butterworth AS5,6, Wang X7, Mahajan A8, Saleheen D5,9,10, Emdin C3,11, Alam D12, Alves AC13, Amouyel P14, Di Angelantonio E5,6, Arveiler D15, Assimes TL16,17, Auer PL18, Baber U19, Ballantyne CM20, Bang LE21, Benn M22,23, Bis JC24, Boehnke M25, Boerwinkle E26,27, Bork-Jensen J28, Bottinger EP29, Brandslund I30,31, Brown M32, Busonero F33, Caulfield MJ32,34,35, Chambers JC36,37,38, Chasman DI39,40, Chen YE41, Chen YI42, Chowdhury R5, Christensen C43, Chu AY39,44, Connell JM45, Cucca F33,46, Cupples LA2,44, Damrauer SM47,48, Davies G49,50, Deary IJ49,50, Dedoussis G51, Denny JC52,53, Dominiczak A54, Dubé MP55,56,57, Ebeling T58, Eiriksdottir G59, Esko T3,60, Farmaki AE51, Feitosa MF61, Ferrario M62, Ferrieres J63, Ford I64, Fornage M65, Franks PW66,67,68, Frayling TM69, Frikke-Schmidt R22,23, Fritsche LG25, Frossard P10, Fuster V19,70, Ganesh SK41,71, Gao W72, Garcia ME73, Gieger C74,75,76, Giulianini F39, Goodarzi MO77,78, Grallert H74,75,76, Grarup N28, Groop L79, Grove ML26, Gudnason V59,80, Hansen T28,81, Harris TB82, Hayward C83, Hirschhorn JN3,84, Holmen OL85,86, Huffman J83, Huo Y87, Hveem K88, Jabeen S10, Jackson AU25, Jakobsdottir J59,89, Jarvelin MR13, Jensen GB90, Jørgensen ME91,92, Jukema JW93,94, Justesen JM28, Kamstrup PR95, Kanoni S96, Karpe F97,98, Kee F99, Khera AV3,11, Klarin D3,11,100, Koistinen HA101,102,103, Kooner JS37,38,104, Kooperberg C105, Kuulasmaa K101, Kuusisto J106, Laakso M106, Lakka T107,108,109, Langenberg C110, Langsted A95,111, Launer LJ82, Lauritzen T112, Liewald DCM49,50, Lin LA65, Linneberg A113,114,115, Loos RJF29,116, Lu Y29, Lu X41,117, Mägi R60, Malarstig A118,119, Manichaikul A120, Manning AK3,11,121, Mäntyselkä P122, Marouli E96, Masca NGD123,124, Maschio A33, Meigs JB3,121,125, Melander O126, Metspalu A60, Morris AP8,127, Morrison AC26, Mulas A33, Müller-Nurasyid M76,128,129, Munroe PB32,35, Neville MJ97, Nielsen JB41, Nielsen SF95,111, Nordestgaard BG95,111, Ordovas JM130,131,132, Mehran R19, O'Donnell CJ100,40, Orho-Melander M126, Molony CM133, Muntendam P134, Padmanabhan S54, Palmer CNA45, Pasko D69, Patel AP3,11,40,135, Pedersen O28, Perola M101,136, Peters A74,76,129, Pisinger C115, Pistis G33, Polasek O137,138, Poulter N139, Psaty BM24,140,141, Rader DJ142, Rasheed A10, Rauramaa R108,109, Reilly DF133, Reiner AP105,143, Renström F66,144, Rich SS120, Ridker PM39, Rioux JD55, Robertson NR8,97, Roden DM52,53, Rotter JI42, Rudan I138, Salomaa V101, Samani NJ123,124, Sanna S33, Sattar N54,97, Schmidt EM145, Scott RA110, Sever P139, Sevilla RS146, Shaffer CM53, Sim X25,147, Sivapalaratnam S148, Small KS149, Smith AV59,80, Smith BH150,151, Somayajula S152, Southam L8,153, Spector TD149, Speliotes EK145,154, Starr JM49,155, Stirrups KE96,156, Stitziel N157,158, Strauch K159,160, Stringham HM25, Surendran P5, Tada H161, Tall AR162, Tang H163, Tardif JC55,57, Taylor KD42, Trompet S93,164, Tsao PS16,17, Tuomilehto J165,166,167,168, Tybjaerg-Hansen A22,23, van Zuydam NR8,45, Varbo A95,111, Varga TV66, Virtamo J101, Waldenberger M75,76,129, Wang N162, Wareham NJ110, Warren HR32,35, Weeke PE53,169, Weinstock J25, Wessel J170,171, Wilson JG172, Wilson PWF173,174, Xu M175, Yaghootkar H69, Young R5, Zeggini E153, Zhang H41, Zheng NS176, Zhang W36, Zhang Y87, Zhou W145, Zhou Y2, Zoledziewska M33; Charge Diabetes Working Group; EPIC-InterAct Consortium; EPIC-CVD Consortium; GOLD Consortium; VA Million Veteran Program, Howson JMM5, Danesh J5,6,153, McCarthy MI8,97,98, Cowan CA4,177, Abecasis G25, Deloukas P96,178, Musunuru K7, Willer CJ41,71,145, Kathiresan S3,11,40,135.

Author information

1
Department of Public Health Sciences, Institute of Personalized Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA.
2
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
3
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
4
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.
5
MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
6
The National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge, Cambridge, UK.
7
Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
9
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
10
Center for Non-Communicable Diseases, Karachi, Pakistan.
11
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
12
ICDDR, B, Dhaka, Bangladesh.
13
Imperial College London, London, UK.
14
Université Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Risk Factors and Molecular Determinants of Aging-related Diseases, Lille, France.
15
Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France.
16
VA Palo Alto Health Care System, Palo Alto, California, USA.
17
Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
18
Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
19
Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
20
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
21
Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
22
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
23
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
24
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
25
Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
26
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, USA.
27
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
28
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
29
The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, New York, USA.
30
Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark.
31
Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
32
Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
33
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.
34
The Barts Heart Centre, William Harvey Research Institute, Queen Mary University of London, London, UK.
35
NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
36
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
37
Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK.
38
Imperial College Healthcare NHS Trust, London, UK.
39
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
40
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
41
Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA.
42
The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Departments of Pediatrics and Medicine, Los Angeles, California, USA.
43
Medical Department, Lillebaelt Hospital, Vejle, Denmark.
44
NHLBI Framingham Heart Study, Framingham, Massachusetts, USA.
45
Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
46
Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy.
47
Corporal Michael Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.
48
Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
49
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
50
Department of Psychology, University of Edinburgh, Edinburgh, UK.
51
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
52
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
53
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
54
British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
55
Montreal Heart Institute, Montreal, Quebec, Canada.
56
Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
57
Université de Montréal, Montreal, Quebec, Canada.
58
Department of Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland.
59
The Icelandic Heart Association, Kopavogur, Iceland.
60
Estonian Genome Center, University of Tartu, Tartu, Estonia.
61
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
62
Research Centre in Epidemiology and Preventive Medicine-EPIMED, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
63
Department of Epidemiology, UMR 1027-INSERM, Toulouse University-CHU Toulouse, Toulouse, France.
64
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
65
Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
66
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
67
Department of Public Health & Clinical Medicine, Umeå University, Umeå, Sweden.
68
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
69
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
70
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
71
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
72
Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China.
73
National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
74
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
75
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
76
Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
77
Departments of Medicine and of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
78
Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA.
79
Department of Clinical Sciences, Diabetes and Endocrinology, Clinical Research Centre, Lund University, Malmö, Sweden.
80
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
81
Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
82
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA.
83
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
84
Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.
85
Department of Public Health and General Practice, HUNT Research Centre, Norwegian University of Science and Technology, Levanger, Norway.
86
St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
87
Department of Cardiology, Peking University First Hospital, Beijing, China.
88
K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
89
Department of Health Sciences, University of Iceland, Reykjavik, Iceland.
90
The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark.
91
Steno Diabetes Center, Gentofte, Denmark.
92
National Institute of Public Health, Southern Denmark University, Copenhagen, Denmark.
93
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
94
The Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
95
Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
96
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
97
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
98
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
99
UKCRC Centre of Excellence for Public Health, Queens University, Belfast, UK.
100
Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts, USA.
101
Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
102
Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
103
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
104
National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK.
105
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
106
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
107
Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.
108
Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
109
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
110
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
111
Faculty of Health and Medical Sciences, University of Denmark, Copenhagen, Denmark.
112
Department of Public Health, Section of General Practice, University of Aarhus, Aarhus, Denmark.
113
Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
114
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
115
Research Center for Prevention and Health, Copenhagen, Denmark.
116
The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, New York, USA.
117
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
118
Cardiovascular Genetics and Genomics Group, Cardiovascular Medicine Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
119
Pharmatherapeutics Clinical Research, Pfizer Worldwide R&D, Sollentuna, Sweden.
120
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
121
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
122
Unit of Primary Health Care, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
123
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
124
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
125
Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
126
Department of Clinical Sciences, University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden.
127
Department of Biostatistics, University of Liverpool, Liverpool, UK.
128
Department of Medicine I, Ludwig-Maximilians-University, Munich, Germany.
129
DZHK German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany.
130
Department of Cardiovascular Epidemiology and Population Genetics, National Center for Cardiovascular Investigation, Madrid, Spain.
131
IMDEA-Alimentacion, Madrid, Spain.
132
Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA.
133
Genetics, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA.
134
G3 Pharmaceuticals, Lexington, Massachusetts, USA.
135
Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
136
Institute of Molecular Medicine FIMM, University of Helsinki, Finland.
137
Faculty of Medicine, University of Split, Split, Croatia.
138
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
139
International Centre for Circulatory Health, Imperial College London, London, UK.
140
Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
141
Departments of Epidemiology and Health Services, University of Washington, Seattle, Washington, USA.
142
Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
143
Department of Epidemiology, University of Washington, Seattle, Washington, USA.
144
Department of Biobank Research, Umeå University, Umeå, Sweden.
145
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
146
Imaging, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA.
147
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
148
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
149
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
150
Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
151
Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
152
Scientific Informatics, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA.
153
Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK.
154
Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.
155
Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
156
Department of Haematology, University of Cambridge, Cambridge, UK.
157
Cardiovascular Division, Departments of Medicine and Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
158
The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
159
IBE, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Germany.
160
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
161
Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
162
Department of Medicine, Division of Molecular Medicine, Columbia University, New York, New York, USA.
163
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
164
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
165
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
166
Dasman Diabetes Institute, Dasman, Kuwait.
167
Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.
168
Saudi Diabetes Research Group, King Abdulaziz University, Fahd Medical Research Center, Jeddah, Saudi Arabia.
169
The Heart Centre, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
170
Department of Epidemiology, Indiana University Fairbanks School of Public Health, Indianapolis, Indiana, USA.
171
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
172
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
173
Atlanta VA Medical Center, Decatur, Georgia, USA.
174
Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia, USA.
175
Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China.
176
Yale College, Yale University, New Haven, Connecticut, USA.
177
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
178
Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

PMID:
29083408
PMCID:
PMC5709146
DOI:
10.1038/ng.3977
[Indexed for MEDLINE]
Free PMC Article

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