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Record W2952687080 · doi:10.1101/257311

Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

2018· preprint· en· W2952687080 on OpenAlexaff
Raymond K. Walters, Mark J. Adams, Amy Adkins, Fazil Alıev, Silviu‐Alin Bacanu, Anthony Batzler, Sarah Bertelsen, Joanna M. Biernacka, Tim B. Bigdeli, Li‐Shiun Chen, Toni‐Kim Clarke, Yi‐Ling Chou, Franziska Degenhardt, Anna R. Docherty, Pierre Fontanillas, Jerome C. Foo, Louis Fox, Josef Frank, Ina Giegling, Scott D. Gordon, Laura M. Hack, Annette M. Hartmann, Sarah M. Hartz, Stefanie Heilmann‐Heimbach, Stefan Herms, Colin A. Hodgkinson, Per Hoffmann, Jouke‐Jan Hottenga, Martin A. Kennedy, Mervi Alanne-Kinnunen, Bettina Konte, Jari Lahti, Marius Lahti‐Pulkkinen, Lannie Ligthart, Anu Loukola, Brion S. Maher, Hamdi Mbarek, Andrew M. McIntosh, Matthew B. McQueen, Yuri Milaneschi, Teemu Palviainen, John F. Pearson, Roseann E. Peterson, Renato Polimanti, Samuli Ripatti, Euijung Ryu, Nancy L. Saccone, Jessica E. Salvatore, Sandra Sanchez‐Roige, Melanie L. Schwandt, Richard Sherva, Fabian Streit, Jana Strohmaier, Nathaniel Thomas, Jen‐Chyong Wang, Bradley T. Webb, Robbee Wedow, Leah Wetherill, Amanda G. Wills, Jason D. Boardman, Danfeng Chen, Doo‐Sup Choi, William Copeland, Robert Culverhouse, Norbert Dahmen, Louisa Degenhardt, Benjamin W. Domingue, Sarah L. Elson, Mark A. Frye, Wolfgang Gäbel, Marcus Ising, Emma C. Johnson, Margaret A. Keyes, Falk Kiefer, John R. Kramer, Samuel Kuperman, Susanne Lucae, Michael T. Lynskey, Wolfgang Maier, Karl Mann, Satu Männistö, Jeanette N. McClintick, Jacquelyn L. Meyers, Bertram Müller‐Myhsok, John I. Nürnberger, Aarno Palotie, Ulrich W. Preuss, Katri Räikkönen, Maureen Reynolds, Monika Ridinger, Norbert Scherbaum, Marc Shuckit, Michael Soyka, Jens Treutlein, Stephanie H. Witt, Norbert Wodarz, Peter Zill, Daniel E. Adkins, Joseph M. Boden, Dorret I. Boomsma, Laura J. Bierut, Sandra A. Brown, Kathleen K. Bucholz, Sven Cichon, E. Jane Costello, Harriet de Wit, Nancy Diazgranados, Danielle M. Dick, Johan G. Eriksson, Lindsay A. Farrer, Tatiana Foroud, Nathan A. Gillespie, Alison Goate, David Goldman, Richard A. Grucza, Dana B. Hancock, Kathleen Mullan Harris, Andrew C. Heath, Victor Hesselbrock, John K. Hewitt, Christian J. Hopfer, L. John Horwood, William G. Iacono, Eric O. Johnson, Jaakko Kaprio, Victor M. Karpyak, Kenneth S. Kendler, Henry R. Kranzler, Kenneth Krauter, Paul Lichtenstein, Penelope A. Lind, Matt McGue, James MacKillop, Pamela A. F. Madden, Hermine H. Maes, Patrik K. E. Magnusson, Nicholas G. Martin, Sarah E. Medland, Grant W. Montgomery, Elliot C. Nelson, Markus M. Nöthen, Abraham A. Palmer, Nancy L. Pedersen, Brenda W.J.H. Penninx, Bernice Porjesz, John P. Rice, Marcella Rietschel, Brien P. Riley, Richard J. Rose, Dan Rujescu, Pei‐Hong Shen, Judy L. Silberg, Michael C. Stallings, Ralph E. Tarter, Michael M. Vanyukov, Scott Vrieze, Tamara L. Wall, John B. Whitfield, Hongyu Zhao, Benjamin M. Neale, Joel Gelernter, Howard J. Edenberg, Arpana Agrawal

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcMaster UniversitySt. Joseph’s Healthcare Hamilton
Fundersnot available
KeywordsGenome-wide association studyGenetic architectureAlcohol dependenceSchizophrenia (object-oriented programming)ADH1BPsychiatryPolygenic risk scoreCannabisAlcohol consumptionGeneticsMedicineBiologyGeneSingle-nucleotide polymorphismAlcoholQuantitative trait locus

Abstract

fetched live from OpenAlex

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 GWAS 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 = 9.8E - 13) and African ancestries (rs2066702; p = 2.2E - 9). Significant genetic correlations were observed with schizophrenia, ADHD, depression, and use of cigarettes and cannabis. There was only modest genetic correlation with alcohol consumption and inconsistent associations with problem drinking. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and non - pathological drinking behaviors.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0050.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.247
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations19
Published2018
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicGenetic Associations and EpidemiologyFrench-language works237,207