Polymorphisms in the Dopamine D4 and D2 Receptor Genes and Reproductive and Sexual Behaviors

Human reproductive and sexual behaviors are heritable and may represent integral life history traits that are likely partially subserved by the dopamine system. Two dopamine receptor polymorphisms, DRD4 48bp VNTR and DRD2 TaqI A, were examined in relation to the Sexual-Orientation Inventory (SOI), age at first sexual intercourse, desired age of marriage, and desired age to have children in 195 (45% male) individuals from a general student population. As DRD4 7R alleles have been associated with migratory behavior, we also examined whether those with more 7R alleles had a greater frequency of multi-racial ancestries. Minor alleles of both polymorphisms (7R and A1 respectively) are believed to decrease the function of their respective receptors. Individuals with DRD4 7R alleles were more likely to have had sexual intercourse and to desire children earlier in life. In addition, DRD4 7R+ individuals were more likely to report multi-racial ancestries. Individuals with DRD2 A1 alleles were more likely to not want children and not want to marry. These results suggest that polymorphisms in the DRD4 and DRD2 genes are meaningfully associated with variation in reproductive and sexual behaviors. These results are provisionally interpreted as consistent with other findings suggesting that DRD4 7R and DRD2 A1 alleles are adaptive for lower offspring investment strategies in dynamic social environments.

[1]  A. Argiolas,et al.  Stimulation of dopamine receptors in the paraventricular nucleus of the hypothalamus of male rats induces penile erection and increases extra-cellular dopamine in the nucleus accumbens: Involvement of central oxytocin , 2007, Neuropharmacology.

[2]  I. Pleština-Borjan,et al.  Long-term exposure to solar ultraviolet radiation as a risk factor for age-related macular degeneration. , 2007, Collegium antropologicum.

[3]  B. Franke,et al.  Behavioral and Brain Functions , 2005 .

[4]  M. Bakermans-Kranenburg,et al.  DRD4 7-repeat polymorphism moderates the association between maternal unresolved loss or trauma and infant disorganization , 2006, Attachment & human development.

[5]  Keith Jones,et al.  Not by genes alone , 2006 .

[6]  M. Caron,et al.  Characterization of the desensitization properties of five dopamine receptor subtypes and alternatively spliced variants of dopamine D2 and D4 receptors. , 2006, Biochemical and biophysical research communications.

[7]  Andrew P Clark Are the correlates of sociosexuality different for men and women , 2006 .

[8]  J. Swanson,et al.  Pharmacogenetics of methylphenidate response in preschoolers with ADHD. , 2006, Journal of the American Academy of Child and Adolescent Psychiatry.

[9]  A. Argiolas,et al.  PIP3EA and PD‐168077, two selective dopamine D4 receptor agonists, induce penile erection in male rats: site and mechanism of action in the brain , 2006, The European journal of neuroscience.

[10]  J. McGeary,et al.  Genetic moderators of naltrexone's effects on alcohol cue reactivity. , 2006, Alcoholism, clinical and experimental research.

[11]  Lin He,et al.  Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). , 2006, Human molecular genetics.

[12]  Edythe D London,et al.  Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. , 2006, Archives of general psychiatry.

[13]  L. Ray,et al.  The Effect of Olanzapine on Craving and Alcohol Consumption , 2006, Neuropsychopharmacology.

[14]  R. Ebstein,et al.  Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual differences in human sexual behavior: desire, arousal and sexual function , 2006, Molecular Psychiatry.

[15]  M. Lehofer,et al.  [35S]GTPgammaS binding at the human dopamine D4 receptor variants hD4.2, hD4.4 and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine. , 2006, European journal of pharmacology.

[16]  B. Aragona,et al.  Dopamine, oxytocin, and vasopressin receptor binding in the medial prefrontal cortex of monogamous and promiscuous voles , 2006, Neuroscience Letters.

[17]  J. Rodgers,et al.  Bio-social determinants of fertility. , 2006, International journal of andrology.

[18]  T. Insel,et al.  Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds , 2006, Nature Neuroscience.

[19]  J. Curtis,et al.  Glucocorticoid receptor involvement in pair bonding in female prairie voles: The effects of acute blockade and interactions with central dopamine reward systems , 2005, Neuroscience.

[20]  Helen E. Fisher,et al.  Romantic love: An fMRI study of a neural mechanism for mate choice , 2005, The Journal of comparative neurology.

[21]  E. Hull,et al.  Dopamine, the medial preoptic area, and male sexual behavior , 2005, Physiology & Behavior.

[22]  H. V. Van Tol,et al.  Folding Efficiency Is Rate-limiting in Dopamine D4 Receptor Biogenesis* , 2005, Journal of Biological Chemistry.

[23]  K. Lesch,et al.  Dopamine and cognitive control: the influence of spontaneous eyeblink rate and dopamine gene polymorphisms on perseveration and distractibility. , 2005, Behavioral neuroscience.

[24]  D. Schmitt Sociosexuality from Argentina to Zimbabwe: A 48-nation study of sex, culture, and strategies of human mating , 2005, Behavioral and Brain Sciences.

[25]  Z. Rónai,et al.  Transmission disequilibrium tests confirm the link between DRD4 gene polymorphism and infant attachment , 2005, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[26]  P. Sullivan,et al.  The use of race variables in genetic studies of complex traits and the goal of reducing health disparities: a transdisciplinary perspective. , 2005, The American psychologist.

[27]  J W Foppe van Mil,et al.  Our Genes , 2005, Pharmacy World and Science.

[28]  P. Richerson,et al.  Not by Genes Alone , 2004 .

[29]  J. Savitz,et al.  Genetic variants implicated in personality: A review of the more promising candidates , 2004, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[30]  M. Neville,et al.  Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1 , 2004, Human mutation.

[31]  J. Swanson,et al.  The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus. , 2004, American journal of human genetics.

[32]  Laurent Gouya,et al.  The 3′ region of the DRD2 gene is involved in genetic susceptibility to schizophrenia , 2004, Schizophrenia Research.

[33]  R. Krueger,et al.  Marriage and personality: a genetic analysis. , 2004, Journal of personality and social psychology.

[34]  James Dermody,et al.  Dopamine receptor 4 (DRD4) 7-repeat allele predicts methylphenidate dose response in children with attention deficit hyperactivity disorder: a pharmacogenetic study. , 2004, Journal of child and adolescent psychopharmacology.

[35]  J. McGeary,et al.  Population stratification in the candidate gene study: fatal threat or red herring? , 2004, Psychological bulletin.

[36]  M. Owen,et al.  Association of the dopamine D4 receptor gene 7-repeat allele with neuropsychological test performance of children with ADHD. , 2004, The American journal of psychiatry.

[37]  J. McGeary,et al.  Olanzapine Reduces Craving for Alcohol: A DRD4 VNTR Polymorphism by Pharmacotherapy Interaction , 2003, Neuropsychopharmacology.

[38]  E. Noble,et al.  D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[39]  D. C. Rowe,et al.  Genetic and Shared Environmental Influences on Adolescents’ Timing of First Sexual Intercourse: The Moderating Effect of Time Spent with a Sibling , 2003 .

[40]  D. Comings,et al.  Evidence of an Emerging Collision Between the Fertility Transition and Genotype-Dependent Fertility Differentials , 2003 .

[41]  O. Schoots,et al.  The human dopamine D4 receptor repeat sequences modulate expression , 2003, The Pharmacogenomics Journal.

[42]  F. Crawford,et al.  DRD4 and novelty seeking: results of meta-analyses. , 2002, American journal of medical genetics.

[43]  P. Gaszner,et al.  Noninvasive genotyping of dopamine receptor D4 (DRD4) using nanograms of DNA from substance-dependent patients. , 2002, Current medicinal chemistry.

[44]  J. McGeary,et al.  The DRD4 VNTR polymorphism moderates craving after alcohol consumption. , 2002, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[45]  K. Hutchison,et al.  The DRD4 VNTR polymorphism influences reactivity to smoking cues. , 2002, Journal of abnormal psychology.

[46]  A. Kluger,et al.  A meta-analysis of the association between DRD4 polymorphism and novelty seeking , 2002, Molecular Psychiatry.

[47]  Z. Rónai,et al.  Further evidence for the role of the dopamine D4 receptor (DRD4) gene in attachment disorganization: interaction of the exon III 48-bp repeat and the −521 C/T promoter polymorphisms , 2002, Molecular Psychiatry.

[48]  J. Swanson,et al.  Evidence of positive selection acting at the human dopamine receptor D4 gene locus , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Odin van der Stelt,et al.  P3 event-related potential, dopamine D2 receptor A1 allele, and sensation-seeking in adult children of alcoholics. , 2001, Alcoholism, clinical and experimental research.

[50]  N. Lavine,et al.  Dopamine D(4) and D(2L) Receptor Stimulation of the Mitogen-Activated Protein Kinase Pathway Is Dependent on trans-Activation of the Platelet-Derived Growth Factor Receptor. , 2001, Molecular pharmacology.

[51]  Thomas J. H. Chen,et al.  The Reward Deficiency Syndrome: A Biogenetic Model for the Diagnosis and Treatment of Impulsive, Addictive and Compulsive Behaviors , 2000, Journal of psychoactive drugs.

[52]  G. Uhl,et al.  Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent in substance abusers: no interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene. , 2000, American journal of medical genetics.

[53]  M I Posner,et al.  Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[54]  T. Insel,et al.  Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster). , 2000, Behavioral neuroscience.

[55]  I. Gottesman,et al.  Endophenotypes for Marital Status in the NAS-NRC Twin Registry , 2000 .

[56]  K. Christensen,et al.  Genetic Influences on Fertility Behavior: Findings From a Danish Twin Study, 1910–1923 , 2000 .

[57]  D. Comings Age at First Childbirth: A Major Selective Factor for Psychiatric Genes in the Twentieth Century , 2000 .

[58]  H. V. Van Tol,et al.  Comparative pharmacological and functional analysis of the human dopamine D4.2 and D4.10 receptor variants. , 1999, Pharmacogenetics.

[59]  Julia Dmitrieva,et al.  Population Migration and the Variation of Dopamine D4 Receptor (DRD4) Allele Frequencies Around the Globe , 1999 .

[60]  J. Rodgers,et al.  Is Fertility Behavior in Our Genes? Findings from a Danish Twin Study , 1999 .

[61]  Warren B. Miller,et al.  DOPAMINE RECEPTOR GENES ARE ASSOCIATED WITH AGE AT FIRST SEXUAL INTERCOURSE , 1999, Journal of Biosocial Science.

[62]  K. Neve,et al.  Short- and long-term heterologous sensitization of adenylate cyclase by D4 dopamine receptors , 1999, Psychopharmacology.

[63]  J. Simpson,et al.  Fluctuating asymmetry, sociosexuality, and intrasexual competitive tactics. , 1999, Journal of personality and social psychology.

[64]  T. Perneger What's wrong with Bonferroni adjustments , 1998, BMJ.

[65]  E K Perry,et al.  D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. , 1997, Pharmacogenetics.

[66]  H. V. Van Tol,et al.  Modulation of Intracellular Cyclic AMP Levels by Different Human Dopamine D4 Receptor Variants , 1995, Journal of neurochemistry.

[67]  A. Argiolas,et al.  Dopamine and sexual behavior , 1995, Neuroscience & Biobehavioral Reviews.

[68]  H. V. Van Tol,et al.  Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes. , 1994, Molecular pharmacology.

[69]  D. Comings,et al.  Association of dopamine D2 receptor gene haplotypes with anovulation and fecundity in female Hispanics. , 1994, Human reproduction.

[70]  L. Mealey,et al.  Heritable and environmental variables affect reproduction-related behaviors, but not ultimate reproductive success , 1993 .

[71]  P. Seeman,et al.  Multiple dopamine D4 receptor variants in the human population , 1992, Nature.

[72]  J. Simpson,et al.  Sociosexuality and Romantic Partner Choice , 1992 .

[73]  J. Simpson,et al.  Individual differences in sociosexuality: evidence for convergent and discriminant validity. , 1991, Journal of personality and social psychology.

[74]  J. Simpson,et al.  Toward an evolutionary history of female sociosexual variation. , 1990, Journal of personality.

[75]  M. Greenwood An Introduction to Medical Statistics , 1932, Nature.