Yihong Zhao1,2, Yongchao Ge3, Zhi-Liang Zheng4. 1. Department of Child and Adolescent Psychiatry, NYU Langone Medical Center, New York, New York. 2. Center for Behavioral Science Research, Department of Health Policy & Health Services Research, Boston University Henry M Goldman School of Dental Medicine, Boston, Massachusetts. 3. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York. 4. Department of Biological Sciences, Lehman College, City University of New York, Bronx, New York.
Abstract
BACKGROUND: Alcohol use disorder (AUD) is a wide-spread, heritable brain disease, but few studies have linked genetic variants or epigenetic factors to brain structures related to AUD in humans, due to many factors including the high-dimensional nature of imaging and genomic data. METHODS: To provide potential insights into the links among epigenetic regulation, brain structure, and AUD, we have performed an integrative analysis of brain structural imaging and blood DNA methylome data from 52 AUD and 58 healthy control (HC) subjects collected in the Nathan Kline Institute-Rockland Sample. RESULTS: We first found that AUD subjects had significantly larger insular surface area than HC in both left and right hemispheres. We then found that 7,827 DNA methylation probes on the HumanMethylation450K BeadChip had significant correlations with the right insular surface area (false discovery rate [FDR] < 0.05). Furthermore, we showed that 44 of the insular surface area-correlated methylation probes were also strongly correlated with AUD status (FDR < 0.05). These AUD-correlated probes are annotated to 36 protein-coding genes, with 16 genes (44%) having been reported by others to be related to AUD or alcohol response, including TAS2R16 and PER2. The remaining 20 genes, in particular ARHGAP22, might represent novel genes involved in AUD or responsive to alcohol. CONCLUSIONS: We have identified 36 insular surface area- and AUD-correlated protein-coding genes that are either known to be AUD- or alcohol-related or not yet reported by prior studies. Therefore, our study suggests that the brain imaging-guided epigenetic analysis has a potential of identifying possible epigenetic mechanisms involved in AUD.
BACKGROUND:Alcohol use disorder (AUD) is a wide-spread, heritable brain disease, but few studies have linked genetic variants or epigenetic factors to brain structures related to AUD in humans, due to many factors including the high-dimensional nature of imaging and genomic data. METHODS: To provide potential insights into the links among epigenetic regulation, brain structure, and AUD, we have performed an integrative analysis of brain structural imaging and blood DNA methylome data from 52 AUD and 58 healthy control (HC) subjects collected in the Nathan Kline Institute-Rockland Sample. RESULTS: We first found that AUD subjects had significantly larger insular surface area than HC in both left and right hemispheres. We then found that 7,827 DNA methylation probes on the HumanMethylation450K BeadChip had significant correlations with the right insular surface area (false discovery rate [FDR] < 0.05). Furthermore, we showed that 44 of the insular surface area-correlated methylation probes were also strongly correlated with AUD status (FDR < 0.05). These AUD-correlated probes are annotated to 36 protein-coding genes, with 16 genes (44%) having been reported by others to be related to AUD or alcohol response, including TAS2R16 and PER2. The remaining 20 genes, in particular ARHGAP22, might represent novel genes involved in AUD or responsive to alcohol. CONCLUSIONS: We have identified 36 insular surface area- and AUD-correlated protein-coding genes that are either known to be AUD- or alcohol-related or not yet reported by prior studies. Therefore, our study suggests that the brain imaging-guided epigenetic analysis has a potential of identifying possible epigenetic mechanisms involved in AUD.
Authors: Laura Saba; Sanjiv V Bhave; Nicholas Grahame; Paula Bice; Razvan Lapadat; John Belknap; Paula L Hoffman; Boris Tabakoff Journal: Mamm Genome Date: 2006-06-12 Impact factor: 2.957
Authors: Danielle M Dick; Kevin Jones; Nancy Saccone; Anthony Hinrichs; Jen C Wang; Alison Goate; Laura Bierut; Laura Almasy; Marc Schuckit; Victor Hesselbrock; Jay Tischfield; Tatiana Foroud; Howard Edenberg; Bernice Porjesz; Henri Begleiter Journal: Behav Genet Date: 2005-12-10 Impact factor: 2.805
Authors: Po-Hsiu Kuo; Michael C Neale; Brien P Riley; Bradley Todd Webb; Patrick F Sullivan; Jen Vittum; Diana G Patterson; Dawn L Thiselton; Edwin J van den Oord; Dermot Walsh; Kenneth S Kendler; Carol A Prescott Journal: Alcohol Clin Exp Res Date: 2006-11 Impact factor: 3.455
Authors: Geoff Joslyn; Ajay Ravindranathan; Gerry Brush; Marc Schuckit; Raymond L White Journal: Alcohol Clin Exp Res Date: 2010-03-01 Impact factor: 3.455
Authors: B Kest; S B Smith; A Schorscher-Petcu; J-S Austin; J Ritchie; G Klein; G C Rossi; A Fortin; J S Mogil Journal: Neuroscience Date: 2009-05-19 Impact factor: 3.590
Authors: An-Yuan Guo; Bradley T Webb; Michael F Miles; Mark P Zimmerman; Kenneth S Kendler; Zhongming Zhao Journal: Nucleic Acids Res Date: 2008-10-31 Impact factor: 16.971
Authors: Steve Horvath; Yafeng Zhang; Peter Langfelder; René S Kahn; Marco P M Boks; Kristel van Eijk; Leonard H van den Berg; Roel A Ophoff Journal: Genome Biol Date: 2012-10-03 Impact factor: 13.583
Authors: Jose Manuel Pérez-García; Fernando Cadaveira; Erick J Canales-Rodríguez; Samuel Suárez-Suárez; Socorro Rodríguez Holguín; Montserrat Corral; Javier Blanco-Ramos; Sonia Doallo Journal: Front Psychiatry Date: 2022-06-23 Impact factor: 5.435