Bio

Bio


Dr. Laura Hack is a Postdoctoral Fellow and Clinical Instructor under the mentorship of Drs. Leanne Williams, Alan Schatzberg, and Ruth O’Hara. She is a translational clinician with a research passion for integrating multiple types of biological and environmental data using advanced analytic techniques into a neuroscience-based taxonomy of mood, anxiety, and stressor-related disorders. Laura envisions herself as a ‘psychiatrist of the future,’ incorporating genetic information, brain imaging, blood-based markers, and data from wearable sensors into diagnostic and treatment decisions to help relieve the suffering that arises from our current trial-and-error approach.

Clinical Focus


  • Psychiatry

Academic Appointments


  • Clinical Instructor, Psychiatry and Behavioral Sciences

Honors & Awards


  • Research Colloquium for Junior Investigators, American Psychiatric Association (2019)
  • Young Investigator Poster Competition, 2nd Place, NEI Congress (2018)
  • Merit based Travel Fellowship Award, Society of Biological Psychiatry (2017)
  • New Investigator Award, American Society of Clinical Psychopharmacology (2017)
  • Psychiatry Resident Research Award, Emory University School of Medicine (2017)
  • Outstanding Resident Award Program, Honorable Mention, NIMH (2016)
  • Phi Kappa Phi Scholarship, Virginia Commonwealth University (2012)
  • Early Career Investigator Program Finalist, World Congress of Psychiatric Genetics (2011)
  • Merit based Alcohol Travel Award, International Society of Psychiatric Genetics (2009)
  • Magna Cum Laude, The College of William & Mary (2006)
  • Senior Thesis Honors in Neuroscience, The College of William & Mary (2006)
  • Summer Research Fellowship, Howard Hughes Medical Institute (2004)
  • James Monroe Scholarship, The College William & Mary (2002)

Professional Education


  • Postdoctoral Research Fellowship, Stanford University (2020)
  • Psychiatry Residency, Emory University School of Medicine (2018)
  • Doctor of Philosophy, Virginia Commonwealth University (2014)
  • Doctor of Medicine, Virginia Commonwealth University (2014)
  • Bachelor of Science, College of William and Mary (2006)

Stanford Advisors


Publications

All Publications


  • Genes, Roommates, and Residence Halls: A Multidimensional Study of the Role of Peer Drinking on College Students' Alcohol Use. Alcoholism, clinical and experimental research Smith, R. L., Salvatore, J. E., Aliev, F., Neale, Z., Barr, P., Dick, D. M. 2019; 43 (6): 1254–62

    Abstract

    Peer drinking is one of the most robust predictors of college students' alcohol use and can moderate students' genetic risk for alcohol use. Peer effect research generally suffers from 2 problems: selection into peer groups and relying more on perceptions of peer alcohol use than peers' self-report. The goal of the present study was to overcome those limitations by capitalizing on a genetically informed sample of randomly assigned college roommates to examine multiple dimensions of peer influence and the interplay between peer effects and genetic predisposition on alcohol use, in the form of polygenic scores.We used a subsample (n = 755) of participants from a university-wide, longitudinal study at a large, diverse, urban university. Participants reported their own alcohol use during fall and spring and their perceptions of college peers' alcohol use in spring. We matched individuals into their rooms and residence halls to create a composite score of peer-reported alcohol use for each of those levels. We examined multiple dimensions of peer influence and whether peer influence moderated genetic predisposition to predict college students' alcohol use using multilevel models to account for clustering at the room and residence hall level.We found that polygenic scores (β = 0.12), perceptions of peer drinking (β = 0.37), and roommates' self-reported drinking (β = 0.10) predicted alcohol use (all ps < 0.001), while average alcohol use across residence hall did not (β = -0.01, p = 0.86). We found no evidence for interactions between peer influence and genome-wide polygenic scores for alcohol use.Our findings underscore the importance of genetic predisposition on individual alcohol use and support the potentially causal nature of the association between peer influence and alcohol use.

    View details for DOI 10.1111/acer.14037

    View details for PubMedID 31034622

    View details for PubMedCentralID PMC6561118

  • Unpacking Genetic Risk Pathways for College Student Alcohol Consumption: The Mediating Role of Impulsivity. Alcoholism, clinical and experimental research Ksinan, A. J., Su, J., Aliev, F., Dick, D. M. 2019

    Abstract

    The period of college represents a particularly risky developmental stage with regard to alcohol use, as college students engage in more risky drinking behaviors than their noncollege peers, and such problematic alcohol use is associated with far-reaching negative consequences. Existing findings from genome-wide association studies (GWAS) indicate that alcohol consumption has a complex polygenic etiology. Currently, there is a lack of studies examining genetic risk for alcohol consumption using polygenic risk scores (PRS) in college samples. In this study, we examined whether alcohol-specific and risky behavior-related PRS were longitudinally associated with alcohol consumption among college students and whether this effect might be partially mediated by impulsivity domains.The sample included n = 2,385 European ancestry (EA) and n = 1,153 African ancestry (AA) college students assessed over the course of 4 years. To indicate genetic risk, 2 PRS were created based on recent large-scale GWAS: alcohol consumption (Liu et al., 2019) -drinks per week (DPW)-PRS and risky behaviors (Linnér et al., 2019) -RISK-PRS. The main outcome was alcohol consumption, measured across 4 waves of follow-up data. The UPPS-P impulsivity subscales were examined as mediators of the genetic effect on alcohol consumption.The results from structural equation modeling showed that among EA students, both DPW-PRS and RISK-PRS had significant positive effects on alcohol consumption above and beyond UPPS dimensions and control variables. RISK-PRS explained larger portion of variance in alcohol consumption than DPW-PRS. RISK-PRS showed a significant indirect effect on alcohol consumption through sensation seeking and lack of perseverance; no significant indirect effect of DPW-PRS was found. No significant association of either PRS or alcohol consumption was found for AA participants.The current results found that PRS related to more broadly defined risky behaviors predicted alcohol consumption across college years and that this association was partially mediated via dimensions of impulsivity.

    View details for DOI 10.1111/acer.14157

    View details for PubMedID 31373688

  • Moving pharmacoepigenetics tools for depression toward clinical use. Journal of affective disorders Hack, L. M., Fries, G. R., Eyre, H. A., Bousman, C. A., Singh, A. B., Quevedo, J., John, V. P., Baune, B. T., Dunlop, B. W. 2019; 249: 336–46

    Abstract

    Major depressive disorder (MDD) is a leading cause of disability worldwide, and over half of patients do not achieve symptom remission following an initial antidepressant course. Despite evidence implicating a strong genetic basis for the pathophysiology of MDD, there are no adequately validated biomarkers of treatment response routinely used in clinical practice. Pharmacoepigenetics is an emerging field that has the potential to combine both genetic and environmental information into treatment selection and further the goal of precision psychiatry. However, this field is in its infancy compared to the more established pharmacogenetics approaches.We prepared a narrative review using literature searches of studies in English pertaining to pharmacoepigenetics and treatment of depressive disorders conducted in PubMed, Google Scholar, PsychINFO, and Ovid Medicine from inception through January 2019. We reviewed studies of DNA methylation and histone modifications in both humans and animal models of depression.Emerging evidence from human and animal work suggests a key role for epigenetic marks, including DNA methylation and histone modifications, in the prediction of antidepressant response. The challenges of heterogeneity of patient characteristics and loci studied as well as lack of replication that have impacted the field of pharmacogenetics also pose challenges to the development of pharmacoepigenetic tools. Additionally, given the tissue specific nature of epigenetic marks as well as their susceptibility to change in response to environmental factors and aging, pharmacoepigenetic tools face additional challenges to their development.This is a narrative and not systematic review of the literature on the pharmacoepigenetics of antidepressant response. We highlight key studies pertaining to pharmacoepigenetics and treatment of depressive disorders in humans and depressive-like behaviors in animal models, regardless of sample size or methodology. While we discuss DNA methylation and histone modifications, we do not cover microRNAs, which have been reviewed elsewhere recently.Utilization of genome-wide approaches and reproducible epigenetic assays, careful selection of the tissue assessed, and integration of genetic and clinical information into pharmacoepigenetic tools will improve the likelihood of developing clinically useful tests.

    View details for PubMedID 30802699

  • Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. Nature neuroscience Walters, R. K., Polimanti, R., Johnson, E. C., McClintick, J. N., Adams, M. J., Adkins, A. E., Aliev, F., Bacanu, S., Batzler, A., Bertelsen, S., Biernacka, J. M., Bigdeli, T. B., Chen, L., Clarke, T., Chou, Y., Degenhardt, F., Docherty, A. R., Edwards, A. C., Fontanillas, P., Foo, J. C., Fox, L., Frank, J., Giegling, I., Gordon, S., Hack, L. M., Hartmann, A. M., Hartz, S. M., Heilmann-Heimbach, S., Herms, S., Hodgkinson, C., Hoffmann, P., Jan Hottenga, J., Kennedy, M. A., Alanne-Kinnunen, M., Konte, B., Lahti, J., Lahti-Pulkkinen, M., Lai, D., Ligthart, L., Loukola, A., Maher, B. S., Mbarek, H., McIntosh, A. M., McQueen, M. B., Meyers, J. L., Milaneschi, Y., Palviainen, T., Pearson, J. F., Peterson, R. E., Ripatti, S., Ryu, E., Saccone, N. L., Salvatore, J. E., Sanchez-Roige, S., Schwandt, M., Sherva, R., Streit, F., Strohmaier, J., Thomas, N., Wang, J., Webb, B. T., Wedow, R., Wetherill, L., Wills, A. G., 23andMe Research Team, Boardman, J. D., Chen, D., Choi, D., Copeland, W. E., Culverhouse, R. C., Dahmen, N., Degenhardt, L., Domingue, B. W., Elson, S. L., Frye, M. A., Gabel, W., Hayward, C., Ising, M., Keyes, M., Kiefer, F., Kramer, J., Kuperman, S., Lucae, S., Lynskey, M. T., Maier, W., Mann, K., Mannisto, S., Muller-Myhsok, B., Murray, A. D., Nurnberger, J. I., Palotie, A., Preuss, U., Raikkonen, K., Reynolds, M. D., Ridinger, M., Scherbaum, N., Schuckit, M. A., Soyka, M., Treutlein, J., Witt, S., Wodarz, N., Zill, P., Adkins, D. E., Boden, J. M., Boomsma, D. I., Bierut, L. J., Brown, S. A., Bucholz, K. K., Cichon, S., Costello, E. J., de Wit, H., Diazgranados, N., Dick, D. M., Eriksson, J. G., Farrer, L. A., Foroud, T. M., Gillespie, N. A., Goate, A. M., Goldman, D., Grucza, R. A., Hancock, D. B., Harris, K. M., Heath, A. C., Hesselbrock, V., Hewitt, J. K., Hopfer, C. J., Horwood, J., Iacono, W., Johnson, E. O., Kaprio, J. A., Karpyak, V. M., Kendler, K. S., Kranzler, H. R., Krauter, K., Lichtenstein, P., Lind, P. A., McGue, M., MacKillop, J., Madden, P. A., Maes, H. H., Magnusson, P., Martin, N. G., Medland, S. E., Montgomery, G. W., Nelson, E. C., Nothen, M. M., Palmer, A. A., Pedersen, N. L., Penninx, B. W., Porjesz, B., Rice, J. P., Rietschel, M., Riley, B. P., Rose, R., Rujescu, D., Shen, P., Silberg, J., Stallings, M. C., Tarter, R. E., Vanyukov, M. M., Vrieze, S., Wall, T. L., Whitfield, J. B., Zhao, H., Neale, B. M., Gelernter, J., Edenberg, H. J., Agrawal, A., Agee, M., Alipanahi, B., Auton, A., Bell, R. K., Bryc, K., Elson, S. L., Fontanillas, P., Furlotte, N. A., Hinds, D. A., Huber, K. E., Kleinman, A., Litterman, N. K., McCreight, J. C., McIntyre, M. H., Mountain, J. L., Noblin, E. S., Northover, C. A., Pitts, S. J., Sathirapongsasuti, J. F., Sazonova, O. V., Shelton, J. F., Shringarpure, S., Tian, C., Tung, J. Y., Vacic, V., Wilson, C. H. 2018; 21 (12): 1656–69

    Abstract

    Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n=46,568; African, n=6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P=9.8*10-13) and African ancestries (rs2066702; P=2.2*10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

    View details for PubMedID 30482948

  • Polyepigenetic Prediction of PTSD Physiology Based on Estrogen Status Seligowski, A., Maddox, S., Jovanovic, T., Michopolous, V., Hack, L., Lori, A., Ressler, K., Smith, A. ELSEVIER SCIENCE INC. 2018: S141
  • Practical outpatient pharmacotherapy for alcohol use disorder. Drugs in context Kim, Y., Hack, L. M., Ahn, E. S., Kim, J. 2018; 7: 212308

    Abstract

    Alcohol use disorder (AUD) is commonly encountered in clinical practice. A combination of psychosocial intervention and pharmacotherapy is the cornerstone of AUD treatment. Despite their efficacy, safety and cost-effectiveness, clinicians are reluctant to prescribe medications to treat individuals with AUD. Given the high rate of relapse with psychosocial intervention alone, increasing patient access to this underutilized treatment has the potential to improve clinical outcome in this difficult-to-treat population. Herein, we provide practical pharmacotherapy strategies to improve treatment outcome for AUD. We review the efficacy and side effects of both on- and off-label agents with a particular focus on clinical applicability. Recommendations are supported by findings from randomized controlled trials (RCT) and meta-analyses selected to be representative, where possible, of current treatment guidelines. The goal of this paper is to help readers use pharmacotherapy with greater confidence when treating patients with AUD.

    View details for DOI 10.7573/dic.212308

    View details for PubMedID 29445407

    View details for PubMedCentralID PMC5804871

  • Suicide Prediction Using Machine Learning Techniques in Screening and Clinician-Derived Data Hack, L., Jovanovic, T., Carter, S., Ressler, K., Smith, A. ELSEVIER SCIENCE INC. 2017: S361
  • Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms. Alcoholism, clinical and experimental research Adkins, A. E., Hack, L. M., Bigdeli, T. B., Williamson, V. S., McMichael, G. O., Mamdani, M., Edwards, A. C., Aliev, F., Chan, R. F., Bhandari, P., Raabe, R. C., Alaimo, J. T., Blackwell, G. G., Moscati, A., Poland, R. S., Rood, B., Patterson, D. G., Walsh, D., Whitfield, J. B., Zhu, G., Montgomery, G. W., Henders, A. K., Martin, N. G., Heath, A. C., Madden, P. A., Frank, J., Ridinger, M., Wodarz, N., Soyka, M., Zill, P., Ising, M., Nöthen, M. M., Kiefer, F., Rietschel, M., Gelernter, J., Sherva, R., Koesterer, R., Almasy, L., Zhao, H., Kranzler, H. R., Farrer, L. A., Maher, B. S., Prescott, C. A., Dick, D. M., Bacanu, S. A., Mathies, L. D., Davies, A. G., Vladimirov, V. I., Grotewiel, M., Bowers, M. S., Bettinger, J. C., Webb, B. T., Miles, M. F., Kendler, K. S., Riley, B. P. 2017; 41 (5): 911–28

    Abstract

    Alcohol dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified.We conducted a genomewide association study in 706 related AD cases and 1,748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms (MOs) to assess the role of orthologous genes in ethanol (EtOH)-response behaviors. We tested 1 primate-specific gene for expression differences in case/control postmortem brain tissue.We detected significant association in COL6A3 and suggestive association in 2 previously implicated loci, KLF12 and RYR3. None of these signals are significant in replication. A suggestive signal in the long noncoding RNA LOC339975 is significant in case:control meta-analysis, but not in a population sample. Knockdown of a COL6A3 ortholog in Caenorhabditis elegans reduced EtOH sensitivity. Col6a3 expression correlated with handling-induced convulsions in mice. Loss of function of the KLF12 ortholog in C. elegans impaired development of acute functional tolerance (AFT). Klf12 expression correlated with locomotor activation following EtOH injection in mice. Loss of function of the RYR3 ortholog reduced EtOH sensitivity in C. elegans and rapid tolerance in Drosophila. The ryanodine receptor antagonist dantrolene reduced motivation to self-administer EtOH in rats. Expression of LOC339975 does not differ between cases and controls but is reduced in carriers of the associated rs11726136 allele in nucleus accumbens (NAc).We detect association between AD and COL6A3, KLF12, RYR3, and LOC339975. Despite nonreplication of COL6A3, KLF12, and RYR3 signals, orthologs of these genes influence behavioral response to EtOH in MOs, suggesting potential involvement in human EtOH response and AD liability. The associated LOC339975 allele may influence gene expression in human NAc. Although the functions of long noncoding RNAs are poorly understood, there is mounting evidence implicating these genes in multiple brain functions and disorders.

    View details for PubMedID 28226201

  • Exposure to Glucocorticoids During Hippocampal Neurogenesis: Effects on DNA Hydroxymethylation Hack, L. M., Provencal, N., Wiechmann, T., Koedel, M., Rex-Haffner, M., Anacker, C., Binder, E. ELSEVIER SCIENCE INC. 2016: 94S
  • Epigenetic mechanisms involved in the effects of stress exposure: focus on 5-hydroxymethylcytosine. Environmental epigenetics Hack, L. M., Dick, A. L., Provençal, N. 2016; 2 (3): dvw016

    Abstract

    5-hydroxymethylcytosine (5hmC) is a recently re-discovered transient intermediate in the active demethylation pathway that also appears to play an independent role in modulating gene function. Epigenetic marks, particularly 5-methylcytosine, have been widely studied in relation to stress-related disorders given the long-lasting effect that stress has on these marks. 5hmC is a good candidate for involvement in the etiology of these disorders given its elevated concentration in mammalian neurons, its dynamic regulation during development of the central nervous system, and its high variability among individuals. Although we are unaware of any studies published to date examining 5 hmC profiles in human subjects who have developed a psychiatric disorder after a life stressor, there is emerging evidence from the animal literature that 5hmC profiles are altered in the context of fear-conditioning paradigms and stress exposure, suggesting a possible role for 5hmC in the biological underpinnings of stress-related disorders. In this review, the authors examine the available approaches for profiling 5hmC and describe their advantages and disadvantages as well as discuss the studies published thus far investigating 5hmC in the context of fear-related learning and stress exposure in animals. The authors also highlight the global versus locus-specific regulation of 5hmC in these studies. Finally, the limitations of the current studies and their implications are discussed.

    View details for DOI 10.1093/eep/dvw016

    View details for PubMedID 29492296

    View details for PubMedCentralID PMC5804530

  • Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence. PloS one Mamdani, M., Williamson, V., McMichael, G. O., Blevins, T., Aliev, F., Adkins, A., Hack, L., Bigdeli, T., van der Vaart, A. D., Web, B. T., Bacanu, S. A., Kalsi, G., Kendler, K. S., Miles, M. F., Dick, D., Riley, B. P., Dumur, C., Vladimirov, V. I. 2015; 10 (9): e0137671

    Abstract

    Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.05). Cell-type-specific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p≤ 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (χ2 test p≤ 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.

    View details for DOI 10.1371/journal.pone.0137671

    View details for PubMedID 26381263

    View details for PubMedCentralID PMC4575063

  • GENOMEWIDE ASSOCIATION STUDY OF ALCOHOL DEPENDENCE IN AN IRISH SAMPLE IDENTIFIES RISK LOCI SUPPORTED BY MODEL ORGANISM STUDIES AND CONVERGENT EVIDENCE Riley, B. P., Adkins, A. E., Hack, L. M., Bigdeli, T. B., Bettinger, J. C., Davies, A. G., Grotewiel, M. S., Prescott, C. A., Dick, D. M., Webb, B. T., Miles, M. F., Kendler, K. S. WILEY-BLACKWELL. 2014: 220A
  • GENOMEWIDE ASSOCIATION STUDY OF ALCOHOL QUANTITATIVE TRAITS IN AN IRISH SAMPLE SUPPORTS THE USE OF PHENOTYPES BEYOND ALCOHOL DEPENDENCE DIAGNOSIS Adkins, A. E., Hack, L. M., Bigdeli, T. B., Bettinger, J. C., Davies, A. G., Grotewiel, M. S., Prescott, C. A., Dick, D. M., Webb, B. T., Miles, M. S., Kendler, K. S., Riley, B. P. WILEY-BLACKWELL. 2014: 309A
  • Summaries from the XIX World Congress of Psychiatric Genetics, Washington, DC, September 10-14, 2011. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics Dai, N., Foldager, L., Gallego, J. A., Hack, L. M., Ji, Y., Lett, T. A., Liu, B. C., Loken, E. K., Mandelli, L., Mehta, D., Power, R. A., Sprooten, E., Stephens, S. H., Paska, A. V., Yan, J., Zai, C. C., Zai, G., Zhang-James, Y., O'Shea, A., Delisi, L. E. 2012; 159B (1): 128–29

    View details for DOI 10.1002/ajmg.b.32017

    View details for PubMedID 22180335

    View details for PubMedCentralID PMC4416401

  • The Effects of leptin on thermosensitive neurons in the anterior hypothalamus of the rat Askin, C. A., Hack, L. M., Griffin, J. D. FEDERATION AMER SOC EXP BIOL. 2011
  • Limited associations of dopamine system genes with alcohol dependence and related traits in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD). Alcoholism, clinical and experimental research Hack, L. M., Kalsi, G., Aliev, F., Kuo, P. H., Prescott, C. A., Patterson, D. G., Walsh, D., Dick, D. M., Riley, B. P., Kendler, K. S. 2011; 35 (2): 376–85

    Abstract

    Over 50 years of evidence from research has established that the central dopaminergic reward pathway is likely involved in alcohol dependence (AD). Additional evidence supports a role for dopamine (DA) in other disinhibitory psychopathology, which is often comorbid with AD. Family and twin studies demonstrate that a common genetic component accounts for most of the genetic variance in these traits. Thus, DA-related genes represent putative candidates for the genetic risk that underlies not only AD but also behavioral disinhibition. Many linkage and association studies have examined these relationships with inconsistent results, possibly because of low power, poor marker coverage, and/or an inappropriate correction for multiple testing.We conducted an association study on the products encoded by 10 DA-related genes (DRD1-D5, SLC18A2, SLC6A3, DDC, TH, COMT) using a large, ethnically homogeneous sample with severe AD (n = 545) and screened controls (n = 509). We collected genotypes from linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (SNPs) and employed a gene-based method of correction. We tested for association with AD diagnosis in cases and controls and with a variety of alcohol-related traits (including age-at-onset, initial sensitivity, tolerance, maximum daily drinks, and a withdrawal factor score), disinhibitory symptoms, and a disinhibitory factor score in cases only. A total of 135 SNPs were genotyped using the Illumina GoldenGate and Taqman Assays-on-Demand protocols.Of the 101 SNPs entered into standard analysis, 6 independent SNPs from 5 DA genes were associated with AD or a quantitative alcohol-related trait. Two SNPs across 2 genes were associated with a disinhibitory symptom count, while 1 SNP in DRD5 was positive for association with the general disinhibitory factor score.Our study provides evidence of modest associations between a small number of DA-related genes and AD as well as a range of alcohol-related traits and measures of behavioral disinhibition. While we did conduct gene-based correction for multiple testing, we did not correct for multiple traits because the traits are correlated. However, false-positive findings remain possible, so our results must be interpreted with caution.

    View details for DOI 10.1111/j.1530-0277.2010.01353.x

    View details for PubMedID 21083670

    View details for PubMedCentralID PMC3443636

  • Effects of leptin on the firing rates of thermoregulatory neurons in the anterior hypothalamus Hack, L. M., Griffin, J. D. FEDERATION AMER SOC EXP BIOL. 2006: A1247