TY - JOUR
T1 - Association of polygenic liability for alcohol dependence and EEG connectivity in adolescence and young adulthood
AU - Meyers, Jacquelyn L.
AU - Chorlian, David B.
AU - Johnson, Emma C.
AU - Pandey, Ashwini K.
AU - Kamarajan, Chella
AU - Salvatore, Jessica E.
AU - Aliev, Fazil
AU - de Viteri, Stacey Subbie Saenz
AU - Zhang, Jian
AU - Chao, Michael
AU - Kapoor, Manav
AU - Hesselbrock, Victor
AU - Kramer, John
AU - Kuperman, Samuel
AU - Nurnberger, John
AU - Tischfield, Jay
AU - Goate, Alison
AU - Foroud, Tatiana
AU - Dick, Danielle M.
AU - Edenberg, Howard J.
AU - Agrawal, Arpana
AU - Porjesz, Bernice
N1 - Funding Information:
Funding: The Collaborative Study on the Genetics of Alcoholism is funded by the National Institutes of Alcohol Abuse and Alcoholism (grant number U10AA08401). In addition, J.L.M is funded by the National Institute of Drug Abuse (grant number K01DA037914). J.E.S is funded by the National Institute of Alcohol Abuse and Alcoholism (grant number K01AA024152), A.A is funded by the National Institute of Drug Abuse (grant number DA32573) and the National Institute of Mental Health (grant number MH109532).
Funding Information:
Acknowledgments: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut, includes 11 different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); 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); Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA (L. Almasy), Virginia Commonwealth University (D. Dick), Icahn School of Medicine at Mount Sinai (A. Goate), and Howard University (R. Taylor). Other COGA collaborators include: L. Bauer (University of Connecticut); J. McClintick, L. Wetherill, X. Xuei, Y. Liu, D. Lai, S. O’Connor, M. Plawecki, S. Lourens (Indiana University); G. Chan (University of Iowa; University of Connecticut); J. Meyers, D. Chorlian, C. Kamarajan, A. Pandey, J. Zhang (SUNY Downstate); J.-C. Wang, M. Kapoor, S. Bertelsen (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); J. Salvatore, F. Aliev, J. Su, S. I-Chun Kuo, B. Cho (Virginia Commonwealth University); and Mark Kos (University of Texas Rio Grande Valley). A. Parsian and H. Chin 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).
Funding Information:
The Collaborative Study on the Genetics of Alcoholism is funded by the National Institutes of Alcohol Abuse and Alcoholism (grant number U10AA08401). In addition, J.L.M is funded by the National Institute of Drug Abuse (grant number K01DA037914). J.E.S is funded by the National Institute of Alcohol Abuse and Alcoholism (grant number K01AA024152), A.A is funded by the National Institute of Drug Abuse (grant number DA32573) and the National Institute of Mental Health (grant number MH109532). Acknowledgments: The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut, includes 11 different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); 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); Department of Biomedical and Health Informatics, The Children?s Hospital of Philadelphia; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA (L. Almasy), Virginia Commonwealth University (D. Dick), Icahn School of Medicine at Mount Sinai (A. Goate), and Howard University (R. Taylor). Other COGA collaborators include: L. Bauer (University of Connecticut); J. McClintick, L. Wetherill, X. Xuei, Y. Liu, D. Lai, S. O?Connor, M. Plawecki, S. Lourens (Indiana University); G. Chan (University of Iowa; University of Connecticut); J. Meyers, D. Chorlian, C. Kamarajan, A. Pandey, J. Zhang (SUNY Downstate); J.-C. Wang, M. Kapoor, S. Bertelsen (Icahn School of Medicine at Mount Sinai); A. Anokhin, V. McCutcheon, S. Saccone (Washington University); J. Salvatore, F. Aliev, J. Su, S. I-Chun Kuo, B. Cho (Virginia Commonwealth University); and Mark Kos (University of Texas Rio Grande Valley). A. Parsian and H. Chin 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).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/10
Y1 - 2019/10
N2 - Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18–31 (beta coefficients ranged from 0.02–0.06, p-values ranged from 10−6–10−12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.
AB - Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18–31 (beta coefficients ranged from 0.02–0.06, p-values ranged from 10−6–10−12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.
KW - AD
KW - AUD
KW - Developmental trajectories
KW - EEG coherence
KW - Neural connectivity
KW - PRS
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85074227531&partnerID=8YFLogxK
U2 - 10.3390/brainsci9100280
DO - 10.3390/brainsci9100280
M3 - Article
AN - SCOPUS:85074227531
SN - 2076-3425
VL - 9
JO - Brain Sciences
JF - Brain Sciences
IS - 10
M1 - 280
ER -