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Hang Zhou, PhD

Assistant Professor of Psychiatry

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Hang Zhou, PhD
Zhou Lab
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Research Summary

My primary research interest is identifying novel genetic risks and exploring the biological etiology for psychiatric diseases and comorbidities.

Extensive Research Description

The central goal of my graduate and postdoctoral work is to understand the human genome and how it affects human traits and diseases. To reach this goal, I completed training in population genetics during PhD and psychiatric genetics as postdoc. I performed a series of genetic studies on natural selection in the human genome and genome-wide studies on substance use disorders (SUDs) and comorbid psychiatric diseases. We were the first to study the shared genetic mechanism for SUDs and major depression comorbidity using genome-wide methods, identified a risk variant (SEMA3A) which specifically contributed to comorbid alcohol use disorder (AUD) and depression (Zhou et al., JAMA Psychiatry, 2017; highlighted by an Editorial paper in JAMA Psychiatry), and a risk variant in GRIA4 gene associated with comorbid nicotine dependence and depression (Zhou et al., Translational Psychiatry, 2018).

I was promoted to Associate Research Scientist in July 2018. During this period, I lead the analytic effort for several projects in the Million Veteran Program (MVP). We conducted the largest multi-ancestry genome-wide association study (GWAS) on alcohol consumption and AUD (Kranzler*, Zhou*, Kember* et al., Nature Communications, 2019), all five major US ancestry groups were included (African Americans, European Americans, Latino Americans, East Asian and South Asian Americans). This study delivered a key message that changed this field: AUD differs from alcohol consumption genetically. We accomplished, to our knowledge, the largest meta-analysis for problematic alcohol use (PAU) in European samples (N=435,563), tripled the number of risk variants associated with PAU (Zhou et al., Nature Neuroscience, 2020). In particular, we found that PAU is genetically correlated with many traits; phenome-wide polygenic risk score (PRS) analysis in an independent biobank (Vanderbilt University Biobank) confirmed the genetic correlations between PAU and substance use and psychiatric disorders; Mendelian randomization (MR) suggested that the liability to PAU was attributable in part to substance use, psychiatric status, risk-taking behavior and cognitive performance; and the genetic heritability of PAU was enriched in certain brain regions. We also conducted the largest-to-date genetic study of opioid use disorder (OUD) and identified functional coding variant Asn40Asp in OPRM1 associated with OUD (Zhou et al., JAMA Psychiatry, 2020). These studies made a noteworthy contribution to this field.

Currently, I am working on multiple projects in MVP, include comorbid AUD and mental disorders, and others. MVP has released the genotype data release 4 containing over 650,000 unique samples, which is presently the world’s largest genomic cohort connected to electronic health record data. I am also working on the whole exome sequencing (WES) data in Yale-Penn cohort (over 4,400 samples) for PAU and comorbid diseases (Brain Behavior Research Foundation 2018 NARSAD Young Investigator Award).

Future research plans

Based on my previous work, my future research will focus on three topics related to alcohol: 1) the genetic causality of alcohol intake and PAU on cancer risk; 2) genetics of sex differences in alcohol use and PAU; 3) advanced genetic study of PAU by incorporating WES, whole genome sequencing (WGS), functional magnetic resonance imaging (fMRI) data, and machine learning methodologies.

Coauthors

Research Interests

Alcoholism; Anxiety Disorders; Depression; Opioid-Related Disorders; Tobacco Use Disorder; Genome-Wide Association Study; Binge Drinking; Whole Genome Sequencing; Whole Exome Sequencing; Human Genetics

Research Images

Causal effects on OUD by Mendelian Randomization analyses.

Selected Publications

  • Genome-wide scan identifies opioid overdose risk locus close to MCOLN1.Cheng Z, Yang BZ, Zhou H, Nunez Y, Kranzler HR, Gelernter J. Genome-wide scan identifies opioid overdose risk locus close to MCOLN1. Addiction Biology 2020, 25: e12811. PMID: 31362332, PMCID: PMC7485539, DOI: 10.1111/adb.12811.
  • Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program.Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF, Stein MB. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. The American Journal Of Psychiatry 2020, 177: 223-232. PMID: 31906708, PMCID: PMC7869502, DOI: 10.1176/appi.ajp.2019.19030256.
  • Functional connectome-wide associations of schizophrenia polygenic risk.Cao H, Zhou H, Cannon TD. Functional connectome-wide associations of schizophrenia polygenic risk. Molecular Psychiatry 2021, 26: 2553-2561. PMID: 32127647, DOI: 10.1038/s41380-020-0699-3.
  • Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits.Zhou H, Sealock JM, Sanchez-Roige S, Clarke TK, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience 2020, 23: 809-818. PMID: 32451486, PMCID: PMC7485556, DOI: 10.1038/s41593-020-0643-5.
  • Association of OPRM1 Functional Coding Variant With Opioid Use Disorder: A Genome-Wide Association Study.Zhou H, Rentsch CT, Cheng Z, Kember RL, Nunez YZ, Sherva RM, Tate JP, Dao C, Xu K, Polimanti R, Farrer LA, Justice AC, Kranzler HR, Gelernter J. Association of OPRM1 Functional Coding Variant With Opioid Use Disorder: A Genome-Wide Association Study. JAMA Psychiatry 2020, 77: 1072-1080. PMID: 32492095, PMCID: PMC7270886, DOI: 10.1001/jamapsychiatry.2020.1206.
  • Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals.Xu K, Li B, McGinnis KA, Vickers-Smith R, Dao C, Sun N, Kember RL, Zhou H, Becker WC, Gelernter J, Kranzler HR, Zhao H, Justice AC. Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals. Nature Communications 2020, 11: 5302. PMID: 33082346, PMCID: PMC7598939, DOI: 10.1038/s41467-020-18489-3.
  • Genetic associations with suicide attempt severity and genetic overlap with major depression.Levey DF, Polimanti R, Cheng Z, Zhou H, Nuñez YZ, Jain S, He F, Sun X, Ursano RJ, Kessler RC, Smoller JW, Stein MB, Kranzler HR, Gelernter J. Genetic associations with suicide attempt severity and genetic overlap with major depression. Translational Psychiatry 2019, 9: 22. PMID: 30655502, PMCID: PMC6336846, DOI: 10.1038/s41398-018-0340-2.
  • Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations.Kranzler HR, Zhou H, Kember RL, Vickers Smith R, Justice AC, Damrauer S, Tsao PS, Klarin D, Baras A, Reid J, Overton J, Rader DJ, Cheng Z, Tate JP, Becker WC, Concato J, Xu K, Polimanti R, Zhao H, Gelernter J. Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nature Communications 2019, 10: 1499. PMID: 30940813, PMCID: PMC6445072, DOI: 10.1038/s41467-019-09480-8.
  • Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.Sun Y, Chang S, Wang F, Sun H, Ni Z, Yue W, Zhou H, Gelernter J, Malison RT, Kalayasiri R, Wu P, Lu L, Shi J. Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison. Translational Psychiatry 2019, 9: 249. PMID: 31591379, PMCID: PMC6779867, DOI: 10.1038/s41398-019-0586-3.
  • Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans.Yang BZ, Zhou H, Cheng Z, Kranzler HR, Gelernter J. Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans. Scientific Reports 2019, 9: 18070. PMID: 31792237, PMCID: PMC6889277, DOI: 10.1038/s41598-019-53560-0.
  • Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans.Cheng Z, Zhou H, Sherva R, Farrer LA, Kranzler HR, Gelernter J. Genome-wide Association Study Identifies a Regulatory Variant of RGMA Associated With Opioid Dependence in European Americans. Biological Psychiatry 2018, 84: 762-770. PMID: 29478698, PMCID: PMC6041180, DOI: 10.1016/j.biopsych.2017.12.016.
  • Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response.Montalvo-Ortiz JL, Zhou H, D'Andrea I, Maroteaux L, Lori A, Smith A, Ressler KJ, Nuñez YZ, Farrer LA, Zhao H, Kranzler HR, Gelernter J. Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response. Molecular Psychiatry 2018, 23: 2277-2286. PMID: 29875475, PMCID: PMC6281782, DOI: 10.1038/s41380-018-0077-6.
  • Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression.Zhou H, Cheng Z, Bass N, Krystal JH, Farrer LA, Kranzler HR, Gelernter J. Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. Translational Psychiatry 2018, 8: 208. PMID: 30287806, PMCID: PMC6172277, DOI: 10.1038/s41398-018-0258-8.
  • Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence.Andersen AM, Pietrzak RH, Kranzler HR, Ma L, Zhou H, Liu X, Kramer J, Kuperman S, Edenberg HJ, Nurnberger JI, Rice JP, Tischfield JA, Goate A, Foroud TM, Meyers JL, Porjesz B, Dick DM, Hesselbrock V, Boerwinkle E, Southwick SM, Krystal JH, Weissman MM, Levinson DF, Potash JB, Gelernter J, Han S. Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence. JAMA Psychiatry 2017, 74: 1153-1160. PMID: 28813562, PMCID: PMC5710224, DOI: 10.1001/jamapsychiatry.2017.2269.
  • Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression.Zhou H, Polimanti R, Yang BZ, Wang Q, Han S, Sherva R, Nuñez YZ, Zhao H, Farrer LA, Kranzler HR, Gelernter J. Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major Depression. JAMA Psychiatry 2017, 74: 1234-1241. PMID: 29071344, PMCID: PMC6331050, DOI: 10.1001/jamapsychiatry.2017.3275.
  • The impact of removing former drinkers from genome-wide association studies of AUDIT-C.Dao C, Zhou H, Small A, Gordon KS, Li B, Kember RL, Ye Y, Gelernter J, Xu K, Kranzler HR, Zhao H, Justice AC. The impact of removing former drinkers from genome-wide association studies of AUDIT-C. Addiction (Abingdon, England) 2021, 116: 3044-3054. PMID: 33861876, DOI: 10.1111/add.15511.
  • Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.Mullins N, Forstner AJ, O'Connell KS, Coombes B, Coleman JRI, Qiao Z, Als TD, Bigdeli TB, Børte S, Bryois J, Charney AW, Drange OK, Gandal MJ, Hagenaars SP, Ikeda M, Kamitaki N, Kim M, Krebs K, Panagiotaropoulou G, Schilder BM, Sloofman LG, Steinberg S, Trubetskoy V, Winsvold BS, Won HH, Abramova L, Adorjan K, Agerbo E, Al Eissa M, Albani D, Alliey-Rodriguez N, Anjorin A, Antilla V, Antoniou A, Awasthi S, Baek JH, Bækvad-Hansen M, Bass N, Bauer M, Beins EC, Bergen SE, Birner A, Bøcker Pedersen C, Bøen E, Boks MP, Bosch R, Brum M, Brumpton BM, Brunkhorst-Kanaan N, Budde M, Bybjerg-Grauholm J, Byerley W, Cairns M, Casas M, Cervantes P, Clarke TK, Cruceanu C, Cuellar-Barboza A, Cunningham J, Curtis D, Czerski PM, Dale AM, Dalkner N, David FS, Degenhardt F, Djurovic S, Dobbyn AL, Douzenis A, Elvsåshagen T, Escott-Price V, Ferrier IN, Fiorentino A, Foroud TM, Forty L, Frank J, Frei O, Freimer NB, Frisén L, Gade K, Garnham J, Gelernter J, Giørtz Pedersen M, Gizer IR, Gordon SD, Gordon-Smith K, Greenwood TA, Grove J, Guzman-Parra J, Ha K, Haraldsson M, Hautzinger M, Heilbronner U, Hellgren D, Herms S, Hoffmann P, Holmans PA, Huckins L, Jamain S, Johnson JS, Kalman JL, Kamatani Y, Kennedy JL, Kittel-Schneider S, Knowles JA, Kogevinas M, Koromina M, Kranz TM, Kranzler HR, Kubo M, Kupka R, Kushner SA, Lavebratt C, Lawrence J, Leber M, Lee HJ, Lee PH, Levy SE, Lewis C, Liao C, Lucae S, Lundberg M, MacIntyre DJ, Magnusson SH, Maier W, Maihofer A, Malaspina D, Maratou E, Martinsson L, Mattheisen M, McCarroll SA, McGregor NW, McGuffin P, McKay JD, Medeiros H, Medland SE, Millischer V, Montgomery GW, Moran JL, Morris DW, Mühleisen TW, O'Brien N, O'Donovan C, Olde Loohuis LM, Oruc L, Papiol S, Pardiñas AF, Perry A, Pfennig A, Porichi E, Potash JB, Quested D, Raj T, Rapaport MH, DePaulo JR, Regeer EJ, Rice JP, Rivas F, Rivera M, Roth J, Roussos P, Ruderfer DM, Sánchez-Mora C, Schulte EC, Senner F, Sharp S, Shilling PD, Sigurdsson E, Sirignano L, Slaney C, Smeland OB, Smith DJ, Sobell JL, Søholm Hansen C, Soler Artigas M, Spijker AT, Stein DJ, Strauss JS, Świątkowska B, Terao C, Thorgeirsson TE, Toma C, Tooney P, Tsermpini EE, Vawter MP, Vedder H, Walters JTR, Witt SH, Xi S, Xu W, Yang JMK, Young AH, Young H, Zandi PP, Zhou H, Zillich L, Adolfsson R, Agartz I, Alda M, Alfredsson L, Babadjanova G, Backlund L, Baune BT, Bellivier F, Bengesser S, Berrettini WH, Blackwood DHR, Boehnke M, Børglum AD, Breen G, Carr VJ, Catts S, Corvin A, Craddock N, Dannlowski U, Dikeos D, Esko T, Etain B, Ferentinos P, Frye M, Fullerton JM, Gawlik M, Gershon ES, Goes FS, Green MJ, Grigoroiu-Serbanescu M, Hauser J, Henskens F, Hillert J, Hong KS, Hougaard DM, Hultman CM, Hveem K, Iwata N, Jablensky AV, Jones I, Jones LA, Kahn RS, Kelsoe JR, Kirov G, Landén M, Leboyer M, Lewis CM, Li QS, Lissowska J, Lochner C, Loughland C, Martin NG, Mathews CA, Mayoral F, McElroy SL, McIntosh AM, McMahon FJ, Melle I, Michie P, Milani L, Mitchell PB, Morken G, Mors O, Mortensen PB, Mowry B, Müller-Myhsok B, Myers RM, Neale BM, Nievergelt CM, Nordentoft M, Nöthen MM, O'Donovan MC, Oedegaard KJ, Olsson T, Owen MJ, Paciga SA, Pantelis C, Pato C, Pato MT, Patrinos GP, Perlis RH, Posthuma D, Ramos-Quiroga JA, Reif A, Reininghaus EZ, Ribasés M, Rietschel M, Ripke S, Rouleau GA, Saito T, Schall U, Schalling M, Schofield PR, Schulze TG, Scott LJ, Scott RJ, Serretti A, Shannon Weickert C, Smoller JW, Stefansson H, Stefansson K, Stordal E, Streit F, Sullivan PF, Turecki G, Vaaler AE, Vieta E, Vincent JB, Waldman ID, Weickert TW, Werge T, Wray NR, Zwart JA, Biernacka JM, Nurnberger JI, Cichon S, Edenberg HJ, Stahl EA, McQuillin A, Di Florio A, Ophoff RA, Andreassen OA. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics 2021, 53: 817-829. PMID: 34002096, PMCID: PMC8192451, DOI: 10.1038/s41588-021-00857-4.
  • Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions.Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.
  • A large-scale genome-wide association study meta-analysis of cannabis use disorder.Johnson EC, Demontis D, Thorgeirsson TE, Walters RK, Polimanti R, Hatoum AS, Sanchez-Roige S, Paul SE, Wendt FR, Clarke TK, Lai D, Reginsson GW, Zhou H, He J, Baranger DAA, Gudbjartsson DF, Wedow R, Adkins DE, Adkins AE, Alexander J, Bacanu SA, Bigdeli TB, Boden J, Brown SA, Bucholz KK, Bybjerg-Grauholm J, Corley RP, Degenhardt L, Dick DM, Domingue BW, Fox L, Goate AM, Gordon SD, Hack LM, Hancock DB, Hartz SM, Hickie IB, Hougaard DM, Krauter K, Lind PA, McClintick JN, McQueen MB, Meyers JL, Montgomery GW, Mors O, Mortensen PB, Nordentoft M, Pearson JF, Peterson RE, Reynolds MD, Rice JP, Runarsdottir V, Saccone NL, Sherva R, Silberg JL, Tarter RE, Tyrfingsson T, Wall TL, Webb BT, Werge T, Wetherill L, Wright MJ, Zellers S, Adams MJ, Bierut LJ, Boardman JD, Copeland WE, Farrer LA, Foroud TM, Gillespie NA, Grucza RA, Harris KM, Heath AC, Hesselbrock V, Hewitt JK, Hopfer CJ, Horwood J, Iacono WG, Johnson EO, Kendler KS, Kennedy MA, Kranzler HR, Madden PAF, Maes HH, Maher BS, Martin NG, McGue M, McIntosh AM, Medland SE, Nelson EC, Porjesz B, Riley BP, Stallings MC, Vanyukov MM, Vrieze S, Davis LK, Bogdan R, Gelernter J, Edenberg HJ, Stefansson K, Børglum AD, Agrawal A. A large-scale genome-wide association study meta-analysis of cannabis use disorder. The Lancet. Psychiatry 2020, 7: 1032-1045. PMID: 33096046, PMCID: PMC7674631, DOI: 10.1016/S2215-0366(20)30339-4.
  • The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates.Hatoum AS, Johnson EC, Colbert SMC, Polimanti R, Zhou H, Walters RK, Gelernter J, Edenberg HJ, Bogdan R, Agrawal A. The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates. Neuropsychopharmacology : Official Publication Of The American College Of Neuropsychopharmacology 2021 PMID: 34750568, DOI: 10.1038/s41386-021-01209-w.
  • Identifying and Reducing Bias in Genome-Wide Association Studies of Alcohol-Related Traits.Kranzler HR, Zhou H, Kember RL. Identifying and Reducing Bias in Genome-Wide Association Studies of Alcohol-Related Traits. The American Journal Of Psychiatry 2022, 179: 14-16. PMID: 34974756, DOI: 10.1176/appi.ajp.2021.21111107.
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