New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders

Evangelos Evangelou^#^{1

2}, He Gao^#^{1

3}, Congying Chu^#⁴, Georgios Ntritsos^#², Paul Blakeley^{1

5}, Andrew R Butts⁶, Raha Pazoki¹, Hideaki Suzuki^{7

8}, Fotios Koskeridis², Andrianos M Yiorkas^{9

10}, Ibrahim Karaman^{1

11}, Joshua Elliott¹, Qiang Luo^{12

13}, Stefanie Aeschbacher¹⁴, Traci M Bartz^{15

16}, Sebastian E Baumeister^{17

18}, Peter S Braund^{19

20}, Michael R Brown²¹, Jennifer A Brody¹⁵, Toni-Kim Clarke²², Niki Dimou², Jessica D Faul²³, Georg Homuth²⁴, Anne U Jackson²⁵, Katherine A Kentistou^{26

27}, Peter K Joshi²⁶, Rozenn N Lemaitre¹⁵, Penelope A Lind²⁸, Leo-Pekka Lyytikäinen^{29

30

31}, Massimo Mangino^{32

33}, Yuri Milaneschi³⁴, Christopher P Nelson^{19

20}, Ilja M Nolte³⁵, Mia-Maria Perälä^{36

37}, Ozren Polasek³⁸, David Porteous^{39

40}, Scott M Ratliff⁴¹, Jennifer A Smith^{23

41}, Alena Stančáková⁴², Alexander Teumer^{17

43}, Samuli Tuominen⁴⁴, Sébastien Thériault^{45

46}, Jagadish Vangipurapu⁴², John B Whitfield⁴⁷, Alexis Wood⁴⁸, Jie Yao⁴⁹, Bing Yu²¹, Wei Zhao⁴¹, Dan E Arking⁵⁰, Juha Auvinen^{51

52}, Chunyu Liu⁵³, Minna Männikkö⁵⁴, Lorenz Risch^{55

56

57}, Jerome I Rotter⁵⁸, Harold Snieder³⁵, Juha Veijola^{59

60

61}, Alexandra I Blakemore^{9

10}, Michael Boehnke²⁵, Harry Campbell²⁶, David Conen⁴⁵, Johan G Eriksson^{62

63

64}, Hans J Grabe^{65

66}, Xiuqing Guo⁴⁹, Pim van der Harst^{67

68

69}, Catharina A Hartman⁷⁰, Caroline Hayward⁷¹, Andrew C Heath⁷², Marjo-Riitta Jarvelin^{73

51

74

75

76}, Mika Kähönen^{77

78}, Sharon L R Kardia⁴¹, Michael Kühne¹⁴, Johanna Kuusisto⁷⁹, Markku Laakso⁷⁹, Jari Lahti⁴⁴, Terho Lehtimäki^{29

30}, Andrew M McIntosh^{22

40}, Karen L Mohlke⁸⁰, Alanna C Morrison²¹, Nicholas G Martin⁴⁷, Albertine J Oldehinkel⁷⁰, Brenda W J H Penninx³⁴, Bruce M Psaty^{81

82}, Olli T Raitakari^{83

84

85}, Igor Rudan²⁶, Nilesh J Samani^{19

20}, Laura J Scott²⁵, Tim D Spector³², Niek Verweij⁶⁷, David R Weir²³, James F Wilson^{26

71}, Daniel Levy^{86

87}, Ioanna Tzoulaki^{1

3}, Jimmy D Bell^#⁸⁸, Paul M Matthews^#^{7

11}, Adrian Rothenfluh^#^{6

89}, Sylvane Desrivières^#⁴, Gunter Schumann^#^{90

91}, Paul Elliott^#^{92

93

94

95

96}

Affiliations

¹ Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
² Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
³ MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
⁴ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁵ NIHR Imperial Biomedical Research Centre, ITMAT Data Science Group, Imperial College London, London, UK.
⁶ Molecular Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
⁷ Centre for Restorative Neurosciences, Division of Brain Sciences, Department of Medicine, Hammersmith Campus, Imperial College London, London, UK.
⁸ Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
⁹ Department of Life Sciences, Brunel University London, London, UK.
¹⁰ Section of Investigative Medicine, Imperial College London, London, UK.
¹¹ UK Dementia Research Institute, Imperial College London, London, UK.
¹² Institute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
¹³ Department of Psychology and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
¹⁴ Cardiology Division, University Hospital Basel, Basel, Switzerland.
¹⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
¹⁷ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
¹⁸ Chair of Epidemiology, Ludwig-Maximilians-Universitat Munchen, UNIKA-T Augsburg, Augsburg, Germany.
¹⁹ Department of Cardiovascular Sciences, University of Leicester, Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK.
²⁰ NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
²¹ Human Genetics Center, Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
²² Department of Psychiatry, University of Edinburgh, Edinburgh, UK.
²³ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
²⁴ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
²⁵ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
²⁶ Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
²⁷ Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
²⁸ Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
²⁹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
³⁰ Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and LHealth Technology, Tampere University, Tampere, Finland.
³¹ Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, Finland.
³² Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
³³ NIHR Biomedical Research Centre, Guy's and St Thomas Foundation Trust, London, UK.
³⁴ Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
³⁵ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
³⁶ Folkhälsan Research Center, Helsinki, Finland.
³⁷ Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
³⁸ Faculty of Medicine, University of Split, Split, Croatia.
³⁹ Generation Scotland, Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
⁴⁰ Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK.
⁴¹ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
⁴² Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
⁴³ German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany.
⁴⁴ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴⁵ Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
⁴⁶ Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec City, Quebec, Canada.
⁴⁷ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁴⁸ Department of Pediatrics/Nutrition, Baylor College of Medicine, Houston, TX, USA.
⁴⁹ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁵⁰ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵¹ Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
⁵² Oulunkaari Health Center, Ii, Finland.
⁵³ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁵⁴ Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland.
⁵⁵ Institute of Clinical Chemistry, Inselspital Bern, University Hospital, University of Bern, Bern, Switzerland.
⁵⁶ Labormedizinisches Zentrum Dr. Risch, Vaduz, Liechtenstein.
⁵⁷ Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
⁵⁸ The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁵⁹ Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland.
⁶⁰ Department of Psychiatry, University Hospital of Oulu, Oulu, Finland.
⁶¹ Medical research Center Oulu, University and University Hospital of Oulu, Oulu, Finland.
⁶² Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁶³ National Institute for Health and Welfare, Helsinki, Finland.
⁶⁴ Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
⁶⁵ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
⁶⁶ German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
⁶⁷ Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁶⁸ Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁶⁹ Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands.
⁷⁰ Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁷¹ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
⁷² Department of Psychiatry, School of Medicine, Washington University in St Louis, St Louis, MO, USA.
⁷³ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
⁷⁴ Biocenter Oulu, University of Oulu, Oulu, Finland.
⁷⁵ Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland.
⁷⁶ Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK.
⁷⁷ Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
⁷⁸ Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁷⁹ Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
⁸⁰ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
⁸¹ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.
⁸² Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
⁸³ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁸⁴ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
⁸⁵ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁸⁶ Framingham Heart Study, Framingham, MA, USA.
⁸⁷ Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁸⁸ Research Centre for Optimal Health, Department of Life Sciences, University of Westminster, London, UK.
⁸⁹ Departments of Psychiatry, Neurobiology & Anatomy, Human Genetics, School of Medicine, University of Utah, Salt Lake City, UT, USA.
⁹⁰ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. gunter.schumann@kcl.ac.uk.
⁹¹ PONS Research Group, Dept of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin, Germany and Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, P.R. China. gunter.schumann@kcl.ac.uk.
⁹² Department of Epidemiology and Biostatistics, Imperial College London, London, UK. p.elliott@imperial.ac.uk.
⁹³ MRC-PHE Centre for Environment and Health, Imperial College London, London, UK. p.elliott@imperial.ac.uk.
⁹⁴ UK Dementia Research Institute, Imperial College London, London, UK. p.elliott@imperial.ac.uk.
⁹⁵ National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare NHS Trust and Imperial College London, London, UK. p.elliott@imperial.ac.uk.
⁹⁶ Health Data Research UK London Substantive Site, London, UK. p.elliott@imperial.ac.uk.

^# Contributed equally.

PMID: 31358974
PMCID: PMC7711277
DOI: 10.1038/s41562-019-0653-z

Meta-Analysis

New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders

Evangelos Evangelou et al. Nat Hum Behav. 2019 Sep.

. 2019 Sep;3(9):950-961.

doi: 10.1038/s41562-019-0653-z. Epub 2019 Jul 29.

Authors

Affiliations

¹ Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
² Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
³ MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
⁴ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁵ NIHR Imperial Biomedical Research Centre, ITMAT Data Science Group, Imperial College London, London, UK.
⁶ Molecular Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
⁷ Centre for Restorative Neurosciences, Division of Brain Sciences, Department of Medicine, Hammersmith Campus, Imperial College London, London, UK.
⁸ Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
⁹ Department of Life Sciences, Brunel University London, London, UK.
¹⁰ Section of Investigative Medicine, Imperial College London, London, UK.
¹¹ UK Dementia Research Institute, Imperial College London, London, UK.
¹² Institute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
¹³ Department of Psychology and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
¹⁴ Cardiology Division, University Hospital Basel, Basel, Switzerland.
¹⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
¹⁷ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
¹⁸ Chair of Epidemiology, Ludwig-Maximilians-Universitat Munchen, UNIKA-T Augsburg, Augsburg, Germany.
¹⁹ Department of Cardiovascular Sciences, University of Leicester, Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK.
²⁰ NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
²¹ Human Genetics Center, Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
²² Department of Psychiatry, University of Edinburgh, Edinburgh, UK.
²³ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
²⁴ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
²⁵ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
²⁶ Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
²⁷ Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
²⁸ Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
²⁹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
³⁰ Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and LHealth Technology, Tampere University, Tampere, Finland.
³¹ Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, Finland.
³² Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
³³ NIHR Biomedical Research Centre, Guy's and St Thomas Foundation Trust, London, UK.
³⁴ Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
³⁵ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
³⁶ Folkhälsan Research Center, Helsinki, Finland.
³⁷ Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.
³⁸ Faculty of Medicine, University of Split, Split, Croatia.
³⁹ Generation Scotland, Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
⁴⁰ Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK.
⁴¹ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
⁴² Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
⁴³ German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany.
⁴⁴ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴⁵ Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
⁴⁶ Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec City, Quebec, Canada.
⁴⁷ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁴⁸ Department of Pediatrics/Nutrition, Baylor College of Medicine, Houston, TX, USA.
⁴⁹ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁵⁰ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵¹ Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
⁵² Oulunkaari Health Center, Ii, Finland.
⁵³ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁵⁴ Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland.
⁵⁵ Institute of Clinical Chemistry, Inselspital Bern, University Hospital, University of Bern, Bern, Switzerland.
⁵⁶ Labormedizinisches Zentrum Dr. Risch, Vaduz, Liechtenstein.
⁵⁷ Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
⁵⁸ The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁵⁹ Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland.
⁶⁰ Department of Psychiatry, University Hospital of Oulu, Oulu, Finland.
⁶¹ Medical research Center Oulu, University and University Hospital of Oulu, Oulu, Finland.
⁶² Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁶³ National Institute for Health and Welfare, Helsinki, Finland.
⁶⁴ Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.
⁶⁵ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
⁶⁶ German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
⁶⁷ Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁶⁸ Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁶⁹ Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands.
⁷⁰ Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁷¹ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
⁷² Department of Psychiatry, School of Medicine, Washington University in St Louis, St Louis, MO, USA.
⁷³ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
⁷⁴ Biocenter Oulu, University of Oulu, Oulu, Finland.
⁷⁵ Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland.
⁷⁶ Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK.
⁷⁷ Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
⁷⁸ Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁷⁹ Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
⁸⁰ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
⁸¹ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.
⁸² Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
⁸³ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁸⁴ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
⁸⁵ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁸⁶ Framingham Heart Study, Framingham, MA, USA.
⁸⁷ Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁸⁸ Research Centre for Optimal Health, Department of Life Sciences, University of Westminster, London, UK.
⁸⁹ Departments of Psychiatry, Neurobiology & Anatomy, Human Genetics, School of Medicine, University of Utah, Salt Lake City, UT, USA.
⁹⁰ Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. gunter.schumann@kcl.ac.uk.
⁹¹ PONS Research Group, Dept of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin, Germany and Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, P.R. China. gunter.schumann@kcl.ac.uk.
⁹² Department of Epidemiology and Biostatistics, Imperial College London, London, UK. p.elliott@imperial.ac.uk.
⁹³ MRC-PHE Centre for Environment and Health, Imperial College London, London, UK. p.elliott@imperial.ac.uk.
⁹⁴ UK Dementia Research Institute, Imperial College London, London, UK. p.elliott@imperial.ac.uk.
⁹⁵ National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare NHS Trust and Imperial College London, London, UK. p.elliott@imperial.ac.uk.
⁹⁶ Health Data Research UK London Substantive Site, London, UK. p.elliott@imperial.ac.uk.

^# Contributed equally.

PMID: 31358974
PMCID: PMC7711277
DOI: 10.1038/s41562-019-0653-z

Abstract

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d^-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.

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Figures

Figure 1.. Manhattan plot showing P-values from discovery genome-wide association meta-analysis with alcohol intake (log g/d) among 480,842 individuals across UK Biobank, AlcGen and CHARGE+, excluding known variants.
The P-value was computed using inverse variance fixed effects models. The y axis shows the –log₁₀ P values and the x axis shows their chromosomal positions. Horizontal blue line represents the threshold of P = 5 × 10⁻⁹.

**Figure 2.. Association of alcohol intake loci with other traits.**
Plot shows results from associations with other traits which were extracted from the PhenoScanner database for the 46 novel sentinel SNPs including proxies in Linkage Disequilibrium (r² ≥ 0.8) with genome-wide significant associations. Each colored line connects a specific variant with the associated traits and diseases.

**Figure 3.. Mediation effect of the grey matter volume of bilateral putamen on the relationship between SNP rs13107325 and alcohol intake.**
The green is for left putamen, and, the red is for the right one. We use ‘a’ for the relationship between rs13107325 and putamen, ‘b’ for the relationship between putamen and alcohol consumption, ‘c’ for the relationship between rs13107325 and alcohol consumption, ‘c” for the relationship between rs13107325 and alcohol consumption after excluding the effect of putamen, and ‘ab’ as the mediation effect. The significance tests are based on the bootstrapping method (10,000 times). Z- statistics and the corresponding P values are provided in parentheses. The brain icon was created using Mango software, version 4.1 (http://ric.uthscsa.edu/mango/).

**Figure 4.. Comparison of *Zip8* alcohol phenotypes in *Drosophila*.**
Flies were exposed to 100/50 Ethanol/Air vapor for 30 min for exposure 1, and the time to 50% loss of righting was determined (ST-50, sedation time). After recovery on food for 4 hours, flies were re-exposed to the same vapors, and the second ST-50 recorded (left side). The resulting increase in ST-50, i.e. tolerance, is shown on the right. In a) overexpressed human *hZIP8* in *ics*-expressing cells flies are compared against controls whereas in b) knockdown of the fly ortholog *dZip71B* is compared against controls. In c) flies carrying two transposon insertions in the endogenous *dZip71B* gene are compared against controls. Significance levels: ***P <0.001, **P <0.01, *P <0.05. Exact P-values are presented in the text.

See this image and copyright information in PMC

References

1. GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 5, 987–1012 (2018). - PMC - PubMed
1. World Health Organization. Global status report on alcohol and health 2018. Eds: Poznyak V and Rekve D, https://www.who.int/substance_abuse/publications/global_alcohol_report/g... (2018).
1. Wood AM et al. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet 391, 1513–1523 (2018). - PMC - PubMed
1. Verhulst B, Neale MC & Kendler KS The heritability of alcohol use disorders: a meta-analysis of twin and adoption studies. Psychol Med 45, 1061–72 (2015). - PMC - PubMed
1. Schumann G et al. KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference. Proc Natl Acad Sci U S A 113, 14372–14377 (2016). - PMC - PubMed

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New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders

Affiliations

New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders

Authors

Affiliations

Abstract

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References

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LinkOut - more resources

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Medical

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