Evaluating risk for alcohol use disorder: Polygenic risk scores and family history

Dongbing Lai; Emma C. Johnson; Sarah Colbert; Gayathri Pandey; Grace Chan; Lance Bauer; Meredith W. Francis; Victor Hesselbrock; Chella Kamarajan; John Kramer; Weipeng Kuang; Sally Kuo; Samuel Kuperman; Yunlong Liu; Vivia McCutcheon; Zhiping Pang; Martin H. Plawecki; Marc Schuckit; Jay Tischfield; Leah Wetherill; Yong Zang; Howard J. Edenberg; Bernice Porjesz; Arpana Agrawal; Tatiana Foroud

doi:10.1111/acer.14772

Evaluating risk for alcohol use disorder: Polygenic risk scores and family history

Dongbing Lai, Emma C. Johnson, Sarah Colbert, Gayathri Pandey, Grace Chan, Lance Bauer, Meredith W. Francis, Victor Hesselbrock, Chella Kamarajan, John Kramer, Weipeng Kuang, Sally Kuo, Samuel Kuperman, Yunlong Liu, Vivia McCutcheon, Zhiping Pang, Martin H. Plawecki, Marc Schuckit, Jay Tischfield, Leah WetherillYong Zang, Howard J. Edenberg, Bernice Porjesz, Arpana Agrawal, Tatiana Foroud

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English
Pages (from-to)	374-383
Number of pages	10
Journal	Alcoholism: Clinical and Experimental Research
Volume	46
Issue number	3
DOIs	https://doi.org/10.1111/acer.14772
State	Published - Mar 2022

Keywords

DSM-5 alcohol use disorder diagnostic criterion count
alcohol use disorders
family history of AUD
polygenic risk scores

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10.1111/acer.14772

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Lai, D., Johnson, E. C., Colbert, S., Pandey, G., Chan, G., Bauer, L., Francis, M. W., Hesselbrock, V., Kamarajan, C., Kramer, J., Kuang, W., Kuo, S., Kuperman, S., Liu, Y., McCutcheon, V., Pang, Z., Plawecki, M. H., Schuckit, M., Tischfield, J., ... Foroud, T. (2022). Evaluating risk for alcohol use disorder: Polygenic risk scores and family history. Alcoholism: Clinical and Experimental Research, 46(3), 374-383. https://doi.org/10.1111/acer.14772

@article{ed9559731ebd4fff95572a340dd47596,

title = "Evaluating risk for alcohol use disorder: Polygenic risk scores and family history",

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.",

keywords = "DSM-5 alcohol use disorder diagnostic criterion count, alcohol use disorders, family history of AUD, polygenic risk scores",

author = "Dongbing Lai and Johnson, {Emma C.} and Sarah Colbert and Gayathri Pandey and Grace Chan and Lance Bauer and Francis, {Meredith W.} and Victor Hesselbrock and Chella Kamarajan and John Kramer and Weipeng Kuang and Sally Kuo and Samuel Kuperman and Yunlong Liu and Vivia McCutcheon and Zhiping Pang and Plawecki, {Martin H.} and Marc Schuckit and Jay Tischfield and Leah Wetherill and Yong Zang and Edenberg, {Howard J.} and Bernice Porjesz and Arpana Agrawal and Tatiana Foroud",

note = "Funding Information: COGA: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, and D. Dick, includes eleven different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, T. Foroud, J. Nurnberger Jr., Y. Liu); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz, J. Meyers, C. Kamarajan, A. Pandey); Washington University in St Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks, R. Hart); The Children{\textquoteright}s Hospital of Philadelphia, University of Pennsylvania (L. Almasy); Virginia Commonwealth University (D. Dick, J. Salvatore); Icahn School of Medicine at Mount Sinai (A. Goate, M. Kapoor, P. Slesinger); and Howard University (D. Scott). Other COGA collaborators include: L. Bauer (University of Connecticut); L. Wetherill, X. Xuei, D. Lai, S. O{\textquoteright}Connor, M.H. Plawecki, S. Lourens (Indiana University); L. Acion (University of Iowa); G. Chan (University of Iowa; University of Connecticut); D.B. Chorlian, J. Zhang, S. Kinreich, G. Pandey (SUNY Downstate); M. Chao (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); F. Aliev, P. Barr (Virginia Commonwealth University); H. Chin and A. Parsian are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting- Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). AA acknowledges funding from MH109532 and K02DA32573. ECJ acknowledges funding from K01DA051759. MWF acknowledges funding from T32DA015035. The authors acknowledge the Indiana University Pervasive Technology Institute for providing [HPC (Big Red II, Karst, Carbonate), visualization, database, storage, or consulting] resources that have contributed to the research results reported within this article. Funding Information: COGA: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, and D. Dick, includes eleven different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, T. Foroud, J. Nurnberger Jr., Y. Liu); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz, J. Meyers, C. Kamarajan, A. Pandey); Washington University in St Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks, R. Hart); The Children{\textquoteright}s Hospital of Philadelphia, University of Pennsylvania (L. Almasy); Virginia Commonwealth University (D. Dick, J. Salvatore); Icahn School of Medicine at Mount Sinai (A. Goate, M. Kapoor, P. Slesinger); and Howard University (D. Scott). Other COGA collaborators include: L. Bauer (University of Connecticut); L. Wetherill, X. Xuei, D. Lai, S. O{\textquoteright}Connor, M.H. Plawecki, S. Lourens (Indiana University); L. Acion (University of Iowa); G. Chan (University of Iowa; University of Connecticut); D.B. Chorlian, J. Zhang, S. Kinreich, G. Pandey (SUNY Downstate); M. Chao (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); F. Aliev, P. Barr (Virginia Commonwealth University); H. Chin and A. Parsian are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co‐PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting‐ Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). AA acknowledges funding from MH109532 and K02DA32573. ECJ acknowledges funding from K01DA051759. MWF acknowledges funding from T32DA015035. The authors acknowledge the Indiana University Pervasive Technology Institute for providing [HPC (Big Red II, Karst, Carbonate), visualization, database, storage, or consulting] resources that have contributed to the research results reported within this article. Publisher Copyright: {\textcopyright} 2022 by the Research Society on Alcoholism",

year = "2022",

month = mar,

doi = "10.1111/acer.14772",

language = "English",

volume = "46",

pages = "374--383",

journal = "Alcoholism: Clinical and Experimental Research",

issn = "0145-6008",

number = "3",

}

Lai, D, Johnson, EC, Colbert, S, Pandey, G, Chan, G, Bauer, L, Francis, MW, Hesselbrock, V, Kamarajan, C, Kramer, J, Kuang, W, Kuo, S, Kuperman, S, Liu, Y, McCutcheon, V, Pang, Z, Plawecki, MH, Schuckit, M, Tischfield, J, Wetherill, L, Zang, Y, Edenberg, HJ, Porjesz, B, Agrawal, A & Foroud, T 2022, 'Evaluating risk for alcohol use disorder: Polygenic risk scores and family history', Alcoholism: Clinical and Experimental Research, vol. 46, no. 3, pp. 374-383. https://doi.org/10.1111/acer.14772

TY - JOUR

T1 - Evaluating risk for alcohol use disorder

T2 - Polygenic risk scores and family history

AU - Lai, Dongbing

AU - Johnson, Emma C.

AU - Colbert, Sarah

AU - Pandey, Gayathri

AU - Chan, Grace

AU - Bauer, Lance

AU - Francis, Meredith W.

AU - Hesselbrock, Victor

AU - Kamarajan, Chella

AU - Kramer, John

AU - Kuang, Weipeng

AU - Kuo, Sally

AU - Kuperman, Samuel

AU - Liu, Yunlong

AU - McCutcheon, Vivia

AU - Pang, Zhiping

AU - Plawecki, Martin H.

AU - Schuckit, Marc

AU - Tischfield, Jay

AU - Wetherill, Leah

AU - Zang, Yong

AU - Edenberg, Howard J.

AU - Porjesz, Bernice

AU - Agrawal, Arpana

AU - Foroud, Tatiana

N1 - Funding Information: COGA: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, and D. Dick, includes eleven different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, T. Foroud, J. Nurnberger Jr., Y. Liu); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz, J. Meyers, C. Kamarajan, A. Pandey); Washington University in St Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks, R. Hart); The Children’s Hospital of Philadelphia, University of Pennsylvania (L. Almasy); Virginia Commonwealth University (D. Dick, J. Salvatore); Icahn School of Medicine at Mount Sinai (A. Goate, M. Kapoor, P. Slesinger); and Howard University (D. Scott). Other COGA collaborators include: L. Bauer (University of Connecticut); L. Wetherill, X. Xuei, D. Lai, S. O’Connor, M.H. Plawecki, S. Lourens (Indiana University); L. Acion (University of Iowa); G. Chan (University of Iowa; University of Connecticut); D.B. Chorlian, J. Zhang, S. Kinreich, G. Pandey (SUNY Downstate); M. Chao (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); F. Aliev, P. Barr (Virginia Commonwealth University); H. Chin and A. Parsian are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting- Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). AA acknowledges funding from MH109532 and K02DA32573. ECJ acknowledges funding from K01DA051759. MWF acknowledges funding from T32DA015035. The authors acknowledge the Indiana University Pervasive Technology Institute for providing [HPC (Big Red II, Karst, Carbonate), visualization, database, storage, or consulting] resources that have contributed to the research results reported within this article. Funding Information: COGA: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, and D. Dick, includes eleven different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, T. Foroud, J. Nurnberger Jr., Y. Liu); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz, J. Meyers, C. Kamarajan, A. Pandey); Washington University in St Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks, R. Hart); The Children’s Hospital of Philadelphia, University of Pennsylvania (L. Almasy); Virginia Commonwealth University (D. Dick, J. Salvatore); Icahn School of Medicine at Mount Sinai (A. Goate, M. Kapoor, P. Slesinger); and Howard University (D. Scott). Other COGA collaborators include: L. Bauer (University of Connecticut); L. Wetherill, X. Xuei, D. Lai, S. O’Connor, M.H. Plawecki, S. Lourens (Indiana University); L. Acion (University of Iowa); G. Chan (University of Iowa; University of Connecticut); D.B. Chorlian, J. Zhang, S. Kinreich, G. Pandey (SUNY Downstate); M. Chao (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); F. Aliev, P. Barr (Virginia Commonwealth University); H. Chin and A. Parsian are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co‐PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting‐ Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). AA acknowledges funding from MH109532 and K02DA32573. ECJ acknowledges funding from K01DA051759. MWF acknowledges funding from T32DA015035. The authors acknowledge the Indiana University Pervasive Technology Institute for providing [HPC (Big Red II, Karst, Carbonate), visualization, database, storage, or consulting] resources that have contributed to the research results reported within this article. Publisher Copyright: © 2022 by the Research Society on Alcoholism

PY - 2022/3

Y1 - 2022/3

N2 - 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.

AB - 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.

KW - DSM-5 alcohol use disorder diagnostic criterion count

KW - alcohol use disorders

KW - family history of AUD

KW - polygenic risk scores

UR - http://www.scopus.com/inward/record.url?scp=85125989417&partnerID=8YFLogxK

U2 - 10.1111/acer.14772

DO - 10.1111/acer.14772

M3 - Article

C2 - 35267208

AN - SCOPUS:85125989417

SN - 0145-6008

VL - 46

SP - 374

EP - 383

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

IS - 3

ER -

Evaluating risk for alcohol use disorder: Polygenic risk scores and family history

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