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Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

ABSTRACT: Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n?=?46,568; African, n?=?6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P?=?9.8?×?10-13) and African ancestries (rs2066702; P?=?2.2?×?10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

SUBMITTER: Walters RK

PROVIDER: S-EPMC6430207 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

Walters Raymond K RK Polimanti Renato R Johnson Emma C EC McClintick Jeanette N JN Adams Mark J MJ Adkins Amy E AE Aliev Fazil F Bacanu Silviu-Alin SA Batzler Anthony A Bertelsen Sarah S Biernacka Joanna M JM Bigdeli Tim B TB Chen Li-Shiun LS Clarke Toni-Kim TK Chou Yi-Ling YL Degenhardt Franziska F Docherty Anna R AR Edwards Alexis C AC Fontanillas Pierre P Foo Jerome C JC Fox Louis L Frank Josef J Giegling Ina I Gordon Scott S Hack Laura M LM Hartmann Annette M AM Hartz Sarah M SM Heilmann-Heimbach Stefanie S Herms Stefan S Hodgkinson Colin C Hoffmann Per P Jan Hottenga Jouke J Kennedy Martin A MA Alanne-Kinnunen Mervi M Konte Bettina B Lahti Jari J Lahti-Pulkkinen Marius M Lai Dongbing D Ligthart Lannie L Loukola Anu A Maher Brion S BS Mbarek Hamdi H McIntosh Andrew M AM McQueen Matthew B MB Meyers Jacquelyn L JL Milaneschi Yuri Y Palviainen Teemu T Pearson John F JF Peterson Roseann E RE Ripatti Samuli S Ryu Euijung E Saccone Nancy L NL Salvatore Jessica E JE Sanchez-Roige Sandra S Schwandt Melanie M Sherva Richard R Streit Fabian F Strohmaier Jana J Thomas Nathaniel N Wang Jen-Chyong JC Webb Bradley T BT Wedow Robbee R Wetherill Leah L Wills Amanda G AG Boardman Jason D JD Chen Danfeng D Choi Doo-Sup DS Copeland William E WE Culverhouse Robert C RC Dahmen Norbert N Degenhardt Louisa L Domingue Benjamin W BW Elson Sarah L SL Frye Mark A MA Gäbel Wolfgang W Hayward Caroline C Ising Marcus M Keyes Margaret M Kiefer Falk F Kramer John J Kuperman Samuel S Lucae Susanne S Lynskey Michael T MT Maier Wolfgang W Mann Karl K Männistö Satu S Müller-Myhsok Bertram B Murray Alison D AD Nurnberger John I JI Palotie Aarno A Preuss Ulrich U Räikkönen Katri K Reynolds Maureen D MD Ridinger Monika M Scherbaum Norbert N Schuckit Marc A MA Soyka Michael M Treutlein Jens J Witt Stephanie S Wodarz Norbert N Zill Peter P Adkins Daniel E DE Boden Joseph M JM Boomsma Dorret I DI Bierut Laura J LJ Brown Sandra A SA Bucholz Kathleen K KK Cichon Sven S Costello E Jane EJ de Wit Harriet H Diazgranados Nancy N Dick Danielle M DM Eriksson Johan G JG Farrer Lindsay A LA Foroud Tatiana M TM Gillespie Nathan A NA Goate Alison M AM Goldman David D Grucza Richard A RA Hancock Dana B DB Harris Kathleen Mullan KM Heath Andrew C AC Hesselbrock Victor V Hewitt John K JK Hopfer Christian J CJ Horwood John J Iacono William W Johnson Eric O EO Kaprio Jaakko A JA Karpyak Victor M VM Kendler Kenneth S KS Kranzler Henry R HR Krauter Kenneth K Lichtenstein Paul P Lind Penelope A PA McGue Matt M MacKillop James J Madden Pamela A F PAF Maes Hermine H HH Magnusson Patrik P Martin Nicholas G NG Medland Sarah E SE Montgomery Grant W GW Nelson Elliot C EC Nöthen Markus M MM Palmer Abraham A AA Pedersen Nancy L NL Penninx Brenda W J H BWJH Porjesz Bernice B Rice John P JP Rietschel Marcella M Riley Brien P BP Rose Richard R Rujescu Dan D Shen Pei-Hong PH Silberg Judy J Stallings Michael C MC Tarter Ralph E RE Vanyukov Michael M MM Vrieze Scott S Wall Tamara L TL Whitfield John B JB Zhao Hongyu H Neale Benjamin M BM Gelernter Joel J Edenberg Howard J HJ Agrawal Arpana A

Nature neuroscience 20181126 12

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were met ...[more]

PMID: 30482948

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Project description:CONTEXT Clinical experience and factor analytic studies suggest that some psychiatric disorders may be more closely related to one another, as indicated by the frequency of their co-occurrence, which may have etiologic and treatment implications. OBJECTIVE To construct a virtual space of common psychiatric disorders, spanned by factors reflecting major psychopathologic dimensions, and locate psychiatric disorders in that space, as well as to examine whether the location of disorders at baseline predicts the prevalence and incidence of disorders at 3-year follow-up. DESIGN, SETTING, AND PATIENTS A total of 34 653 individuals participated in waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. MAIN OUTCOME MEASURES The distance between disorders at wave 1, calculated using the loadings of the factors spanning the space of disorders as coordinates. This distance was correlated with the adjusted odds ratios for age, sex, and race/ethnicity of the prevalence and incidence of Axis I disorders in wave 2, with the aim of determining whether smaller distances between disorders at wave 1 predicts higher disorder prevalence and incidence at wave 2. RESULTS A model with 3 correlated factors provided an excellent fit (Comparative Fit Index = 0.99, Tucker-Lewis Index = 0.98, root mean square error of approximation = 0.008) for the structure of common psychiatric disorders and was used to span the space of disorders. Distances ranged from 0.070 (between drug abuse and alcohol dependence) to 1.032 (between drug abuse and dysthymia). The correlation of distance between disorders in wave 1 with adjusted odds ratios of prevalence in wave 2 was -0.56. The correlation of distance in wave 1 with adjusted odds ratios of incidence in wave 2 was -0.57. CONCLUSIONS Mapping psychiatric disorders can be used to quantify the distances among disorders. Proximity in turn can be used to predict prospectively the incidence and prevalence of Axis I disorders.

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Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

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Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

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