Dongbing Lai1, Emma C Johnson2, Sarah Colbert2, Gayathri Pandey3, Grace Chan4,5, Lance Bauer4, Meredith W Francis6, Victor Hesselbrock4, Chella Kamarajan3, John Kramer5, Weipeng Kuang3, Sally Kuo7, Samuel Kuperman5, Yunlong Liu1, Vivia McCutcheon2, Zhiping Pang8, Martin H Plawecki9, Marc Schuckit10, Jay Tischfield11, Leah Wetherill1, Yong Zang12, Howard J Edenberg1,13, Bernice Porjesz3, Arpana Agrawal2, Tatiana Foroud1. 1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA. 2. Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA. 3. Henri Begleiter Neurodynamics Lab, Department of Psychiatry, Downstate Medical Center, State University of New York, Brooklyn, New York, USA. 4. Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut, USA. 5. Department of Psychiatry, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa, USA. 6. The Brown School of Social Work, Washington University School of Medicine, St Louis, Missouri, USA. 7. Department of Psychology, Virginia Commonwealth University, Richmond, Virginia, USA. 8. Department of Neuroscience and Cell Biology, Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. 9. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA. 10. Department of Psychiatry, University of California, San Diego Medical School, San Diego, California, USA. 11. Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey, USA. 12. Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA. 13. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract
BACKGROUND: Early identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM-5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD. METHODS: We studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM-IV alcohol dependence or DSM-5 AUD and 1616 were alcohol-exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first-degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH-). PRS were derived from a meta-analysis of a genome-wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity. RESULTS: AUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E-05 ) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p-value = 7.57E-08 ) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E-04 ) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first-degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM-5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p-values ≤6.7E-11 ). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E-10 ). CONCLUSIONS: Both PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits.
BACKGROUND: Early identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM-5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD. METHODS: We studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM-IV alcohol dependence or DSM-5 AUD and 1616 were alcohol-exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first-degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH-). PRS were derived from a meta-analysis of a genome-wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity. RESULTS: AUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E-05 ) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p-value = 7.57E-08 ) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E-04 ) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first-degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM-5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p-values ≤6.7E-11 ). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E-10 ). CONCLUSIONS: Both PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits.
Authors: Dongbing Lai; Leah Wetherill; Sarah Bertelsen; Caitlin E Carey; Chella Kamarajan; Manav Kapoor; Jacquelyn L Meyers; Andrey P Anokhin; David A Bennett; Kathleen K Bucholz; Katharine K Chang; Philip L De Jager; Danielle M Dick; Victor Hesselbrock; John Kramer; Samuel Kuperman; John I Nurnberger; Towfique Raj; Marc Schuckit; Denise M Scott; Robert E Taylor; Jay Tischfield; Ahmad R Hariri; Howard J Edenberg; Arpana Agrawal; Ryan Bogdan; Bernice Porjesz; Alison M Goate; Tatiana Foroud Journal: Genes Brain Behav Date: 2019-06-04 Impact factor: 3.449
Authors: Mari E K Niemi; Hilary C Martin; Daniel L Rice; Giuseppe Gallone; Scott Gordon; Martin Kelemen; Kerrie McAloney; Jeremy McRae; Elizabeth J Radford; Sui Yu; Jozef Gecz; Nicholas G Martin; Caroline F Wright; David R Fitzpatrick; Helen V Firth; Matthew E Hurles; Jeffrey C Barrett Journal: Nature Date: 2018-09-26 Impact factor: 49.962
Authors: Henry R Kranzler; Hang Zhou; Rachel L Kember; Rachel Vickers Smith; Amy C Justice; Scott Damrauer; Philip S Tsao; Derek Klarin; Aris Baras; Jeffrey Reid; John Overton; Daniel J Rader; Zhongshan Cheng; Janet P Tate; William C Becker; John Concato; Ke Xu; Renato Polimanti; Hongyu Zhao; Joel Gelernter Journal: Nat Commun Date: 2019-04-02 Impact factor: 14.919
Authors: Matthew Moll; Sharon M Lutz; Auyon J Ghosh; Phuwanat Sakornsakolpat; Craig P Hersh; Terri H Beaty; Frank Dudbridge; Martin D Tobin; Murray A Mittleman; Edwin K Silverman; Brian D Hobbs; Michael H Cho Journal: BMJ Open Respir Res Date: 2020-11
Authors: Sandra Sanchez-Roige; Abraham A Palmer; Pierre Fontanillas; Sarah L Elson; Mark J Adams; David M Howard; Howard J Edenberg; Gail Davies; Richard C Crist; Ian J Deary; Andrew M McIntosh; Toni-Kim Clarke Journal: Am J Psychiatry Date: 2018-10-19 Impact factor: 18.112
Authors: Tuomo Kiiskinen; Nina J Mars; Teemu Palviainen; Jukka Koskela; Joel T Rämö; Pietari Ripatti; Sanni Ruotsalainen; Aarno Palotie; Pamela A F Madden; Richard J Rose; Jaakko Kaprio; Veikko Salomaa; Pia Mäkelä; Aki S Havulinna; Samuli Ripatti Journal: Transl Psychiatry Date: 2020-01-21 Impact factor: 6.222
Authors: Dongbing Lai; Tae-Hwi Schwantes-An; Marco Abreu; Grace Chan; Victor Hesselbrock; Chella Kamarajan; Yunlong Liu; Jacquelyn L Meyers; John I Nurnberger; Martin H Plawecki; Leah Wetherill; Marc Schuckit; Pengyue Zhang; Howard J Edenberg; Bernice Porjesz; Arpana Agrawal; Tatiana Foroud Journal: Transl Psychiatry Date: 2022-07-05 Impact factor: 7.989
Authors: Nathaniel S Thomas; Jessica E Salvatore; Sally I-Chun Kuo; Fazil Aliev; Vivia V McCutcheon; Jacquelyn M Meyers; Kathleen K Bucholz; Sarah J Brislin; Grace Chan; Howard J Edenberg; Chella Kamarajan; John R Kramer; Samuel Kuperman; Gayathri Pandey; Martin H Plawecki; Marc A Schuckit; Danielle M Dick Journal: Mol Psychiatry Date: 2022-10-17 Impact factor: 13.437