CHRNA 5 and CHRNA 3 Variants and Level of Neuroticism in Young Adult Mexican American Men and Women

A lifetime history of alcohol dependence has been associated with elevations in neuroticism in Mexican American young adults. The identification of genetic markers associated with neuroticism and their influence on the development of alcohol use disorders (AUD) may contribute to our understanding of the relationship between personality traits and the increased risk of AUD in Mexican Americans. The purpose of this study was to investigate associations between neuroticism and 13 single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine (nAChR) 5-subunit (CHRNA5) and 3-subunit (CHRNA3) genes in young adult Mexican American men and women. Participants were 465 young adult Mexican American men and women who are literate in English and are residing legally in San Diego County. Each participant gave a blood sample and completed a structured diagnostic interview. Neuroticism was assessed using the Maudsley Personality Inventory. The minor alleles of four CHRNA5 polymorphisms (rs588765, rs601079, rs680244 and rs555018) and three CHRNA3 polymorphisms (rs578776, rs6495307 and rs3743078) showed associations with neuroticism. Several of these SNPs also displayed nominal associations with DSM-IV alcohol and nicotine dependence, but tests of mediation suggested that these relations could be partially explained by the presence of co-occurring neuroticism. These findings suggest that genetic variations in nicotinic receptor genes may influence the development of neuroticism, which in turn is involved in the development of AUDs and nicotine dependence in Mexican American young adults.

[1]  C. Ehlers,et al.  ADH and ALDH Polymorphisms and Alcohol Dependence in Mexican and Native Americans , 2012, The American journal of drug and alcohol abuse.

[2]  Sarah H. Stephens,et al.  Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers. , 2012, Archives of general psychiatry.

[3]  J. Mintz,et al.  Neuroticism, acculturation and the cortisol awakening response in Mexican American adults , 2012, Hormones and Behavior.

[4]  C. D. Fowler,et al.  Recent advances in understanding nicotinic receptor signaling mechanisms that regulate drug self-administration behavior. , 2011, Biochemical pharmacology.

[5]  C. Ehlers,et al.  N4 component responses to pre-pulse startle stimuli in young adults: Relationship to alcohol dependence , 2011, Psychiatry Research.

[6]  J Blangero,et al.  Common genetic influences on depression, alcohol, and substance use disorders in Mexican‐American families , 2011, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[7]  R. Hurst,et al.  Partial Agonists of the α3β4* Neuronal Nicotinic Acetylcholine Receptor Reduce Ethanol Consumption and Seeking in Rats , 2011, Neuropsychopharmacology.

[8]  R. Caetano,et al.  The Hispanic Americans Baseline Alcohol Survey (HABLAS): Alcohol consumption and sociodemographic predictors across Hispanic national groups , 2010, Journal of substance use.

[9]  C. Ehlers,et al.  Genome-wide scan for self-rating of the effects of alcohol in American Indians , 2010, Psychiatric genetics.

[10]  William Wheeler,et al.  Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD , 2010, PLoS genetics.

[11]  D. Oslin,et al.  Variation in Nicotinic Acetylcholine Receptor Genes is Associated with Multiple Substance Dependence Phenotypes , 2010, Neuropsychopharmacology.

[12]  C. Gieger,et al.  Sequence variants at CHRNB3–CHRNA6 and CYP2A6 affect smoking behavior , 2010, Nature Genetics.

[13]  Ming D. Li,et al.  Genome-wide meta-analyses identify multiple loci associated with smoking behavior , 2010, Nature Genetics.

[14]  C. Ehlers,et al.  EEG alpha phenotypes: linkage analyses and relation to alcohol dependence in an American Indian community study , 2010, BMC Medical Genetics.

[15]  S. Bartlett,et al.  Neuronal nicotinic acetylcholine receptors as pharmacotherapeutic targets for the treatment of alcohol use disorders. , 2010, CNS & neurological disorders drug targets.

[16]  C. Ehlers,et al.  Acculturation Stress, Anxiety Disorders, and Alcohol Dependence in a Select Population of Young Adult Mexican Americans , 2009, Journal of addiction medicine.

[17]  E. Erdfelder,et al.  Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses , 2009, Behavior research methods.

[18]  Scott F. Saccone,et al.  The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. , 2009, Cancer research.

[19]  Scott F. Saccone,et al.  Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. , 2009, Human molecular genetics.

[20]  Scott F. Saccone,et al.  Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence , 2009, Molecular Psychiatry.

[21]  Raymond L. White,et al.  Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans , 2008, Proceedings of the National Academy of Sciences.

[22]  Tatiana Foroud,et al.  Variants in nicotinic receptors and risk for nicotine dependence. , 2008, The American journal of psychiatry.

[23]  A. C. Collins,et al.  The CHRNA5/A3/B4 Gene Cluster Variability as an Important Determinant of Early Alcohol and Tobacco Initiation in Young Adults , 2008, Biological Psychiatry.

[24]  R. Caetano,et al.  The Hispanic Americans Baseline Alcohol Survey (HABLAS): rates and predictors of alcohol abuse and dependence across Hispanic national groups. , 2008, Journal of studies on alcohol and drugs.

[25]  Corinna E Löckenhoff,et al.  Five-Factor Model personality profiles of drug users , 2008, BMC psychiatry.

[26]  R. Caetano,et al.  The Hispanic Americans Baseline Alcohol Survey (HABLAS): Rates and predictors of DUI across Hispanic national groups. , 2008, Accident; analysis and prevention.

[27]  T. Heeren,et al.  Country of origin, age of drinking onset, and drinking patterns among Mexican American young adults. , 2007, Drug and alcohol dependence.

[28]  C. Ehlers,et al.  Electrophysiological responses to affective stimuli in Mexican Americans: Relationship to alcohol dependence and personality traits , 2007, Pharmacology Biochemistry and Behavior.

[29]  C. Ehlers,et al.  Association of EEG alpha variants and alpha power with alcohol dependence in Mexican American young adults. , 2007, Alcohol.

[30]  K. Sher,et al.  Family history of alcoholism and the stability of personality in young adulthood. , 2006, Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors.

[31]  J. Read,et al.  High- and low-dose expectancies as mediators of personality dimensions and alcohol involvement. , 2006, Journal of studies on alcohol.

[32]  J. Malouff,et al.  The Five-Factor Model of Personality and Smoking: A Meta-Analysis , 2006, Journal of drug education.

[33]  C. Nemeroff,et al.  DO HOSTILITY AND NEUROTICISM CONFOUND ASSOCIATIONS BETWEEN PERCEIVED DISCRIMINATION AND DEPRESSIVE SYMPTOMS , 2005 .

[34]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[35]  B. Grant,et al.  Immigration and lifetime prevalence of DSM-IV psychiatric disorders among Mexican Americans and non-Hispanic whites in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. , 2004, Archives of general psychiatry.

[36]  Antonio Terracciano,et al.  Smoking and the Five-Factor Model of personality. , 2004, Addiction.

[37]  K. Kendler,et al.  The interrelationship of neuroticism, sex, and stressful life events in the prediction of episodes of major depression. , 2004, The American journal of psychiatry.

[38]  K. Jackson,et al.  Alcohol use disorders and psychological distress: a prospective state-trait analysis. , 2003, Journal of abnormal psychology.

[39]  R. Roberts,et al.  The impact of multiple dimensions of ethnic identity on discrimination and adolescents' self-esteem. , 2003 .

[40]  W. Sribney,et al.  Co-occurring alcohol, drug, and other psychiatric disorders among Mexican-origin people in the United States. , 2003, American journal of public health.

[41]  C. Robert Cloninger,et al.  Measurement of Impulsivity in a Hierarchical Model of Personality Traits: Implications for Substance Use , 2003, Substance use & misuse.

[42]  R. Demmel.  Psychological theories of drinking and alcoholism. , 2002 .

[43]  J Ormel,et al.  The interplay and etiological continuity of neuroticism, difficulties, and life events in the etiology of major and subsyndromal, first and recurrent depressive episodes in later life. , 2001, The American journal of psychiatry.

[44]  R. Rosenheck,et al.  Acculturation and the lifetime risk of psychiatric and substance use disorders among Hispanics. , 2000, The Journal of nervous and mental disease.

[45]  K. Sher,et al.  Personality and substance use disorders: a prospective study. , 2000, Journal of consulting and clinical psychology.

[46]  K. Matheny,et al.  Socio-Psychological Predictors of Acculturative Stress among Latino Adults , 2000 .

[47]  B. Finch,et al.  Perceived discrimination and depression among Mexican-origin adults in California. , 2000, Journal of health and social behavior.

[48]  A. L. Nielsen.  Examining drinking patterns and problems among hispanic groups: results from a national survey. , 2000, Journal of studies on alcohol.

[49]  M. Hesselbrock,et al.  A validity study of the SSAGA--a comparison with the SCAN. , 1999, Addiction.

[50]  D. Dawson,et al.  Beyond black, white and Hispanic: race, ethnic origin and drinking patterns in the United States. , 1998, Journal of substance abuse.

[51]  J. Caraveo-Anduaga,et al.  Lifetime prevalence of DSM-III-R psychiatric disorders among urban and rural Mexican Americans in California. , 1998, Archives of general psychiatry.

[52]  J. Escobar,et al.  Immigration and mental health: why are immigrants better off? , 1998, Archives of general psychiatry.

[53]  R A McCormick,et al.  The relationship of NEO-PI performance to coping styles, patterns of use, and triggers for use among substance abusers. , 1998, Addictive behaviors.

[54]  I. Sutherland.  The development and application of a questionnaire to assess the changing personalities of substance addicts during the first year of recovery. , 1997, Journal of clinical psychology.

[55]  K. Kendler,et al.  Predictors of problem drinking and alcohol dependence in a population-based sample of female twins. , 1997, Journal of studies on alcohol.

[56]  R. Pihl,et al.  Alcoholism: the role of different motivational systems. , 1995, Journal of psychiatry & neuroscience : JPN.

[57]  J. Rice,et al.  Comparison of direct interview and family history diagnoses of alcohol dependence. , 1995, Alcoholism, clinical and experimental research.

[58]  J. Nurnberger,et al.  A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. , 1994, Journal of studies on alcohol.

[59]  T. Trull,et al.  Personality and disinhibitory psychopathology: alcoholism and antisocial personality disorder. , 1994, Journal of abnormal psychology.

[60]  J. Golding.  Immigration, Stress, and Depressive Symptoms in a Mexican-American Community , 1990, The Journal of nervous and mental disease.

[61]  C. Robert Cloninger,et al.  Childhood personality predicts alcohol abuse in young adults. , 1988, Alcoholism, clinical and experimental research.

[62]  A. Padilla,et al.  Acculturative Stress and Specific Coping Strategies among Immigrant and Later Generation College Students , 1987 .

[63]  M. Burnam,et al.  Acculturation and lifetime prevalence of psychiatric disorders among Mexican Americans in Los Angeles. , 1987, Journal of health and social behavior.

[64]  C. Gieger,et al.  Sequence variants at CHRNB 3 – CHRNA 6 and CYP 2 A 6 affect smoking behavior , 2010 .

[65]  Kenneth J Sher,et al.  The development of alcohol use disorders. , 2005, Annual review of clinical psychology.

[66]  R. Kessler,et al.  Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. , 1994, Archives of general psychiatry.

[67]  D. A. Kenny,et al.  The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. , 1986, Journal of personality and social psychology.

[68]  G. Claridge.  Manual of the Eysenck personality questionnaire (junior and adult): H. J. Eysenck and Sybil Eysenck Hodder and Stoughton (1975). 47 pp., together with test blanks and scoring keys for junior and adult versions. Specimen set £1.80 , 1977 .