The DRD2 gene in psychiatric and neurological disorders and its phenotypes

Pharmacogenomics

Volumn 1, Issue 3, 2000, Pages 309-333

  Noble, Ernest P ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Alcoholism; Association; D2 dopamine receptor gene; DRD2 A1 allele; Linkage; Neuropsychiatric disorders; Pharmacogenomics; Polymorphism; Substance abuse

Indexed keywords

DOPAMINE 2 RECEPTOR;

ANIMAL; DRUG EFFECT; GENETICS; HUMAN; MENTAL DISEASE; METABOLISM; NEUROLOGIC DISEASE; PHENOTYPE; REVIEW;

ANIMALS; HUMANS; MENTAL DISORDERS; NERVOUS SYSTEM DISEASES; PHENOTYPE; RECEPTORS, DOPAMINE D2;

EID: 0034252558     PISSN: 14622416     EISSN: None     Source Type: Journal    
DOI: 10.1517/14622416.1.3.309     Document Type: Review

References (157)

1. EGELAND JA, GERHARD DS, PAULS DL et al.: Bipolar affective disorders linked to DNA markers on chromosome 11. Nature (1987) 325:783-787.
2. BARON M, RISCH N, HAMBURGER K et al.: Genetic linkage between X-chromosome markers and bipolar affective illness. Nature (1987) 326:289-292.
3. SHERRINGTON R, BRYNJOLFSSON J, PETURSSON H et al.: Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature (1988) 336:164-167.
4. KELSO JR, GINNS EI, EGELAND JA et al.: Reevaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature (1989) 342:238-243.
5. PLOMIN R: The role of inheritance in behavior. Science (1990) 248:183-186.
6. OWEN MJ, CARDNO AG, O'DONOVAN MC: Psychiatric genetics: back to the future. Psychiatr. Genet. (2000) 5:22-31.
7. BENNETT ST, LUCASSEN AM, GOUGH SC et al.: Susceptibility to human Type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nat. Genet. (1995) 9:284-292.
8. GOODWIN DW: Alcoholism and heredity. Arch. Gen. Psychiatry (1979) 36:57-61. • Review on the role of family, twin and adoption studies in alcoholism.
9. CLONINGER CR, BOHMAN M, SIGVARDSSON S: Inheritance of alcohol abuse. Arch. Gen. Psychiatry (1981) 38:861-868.
10. PICKENS RW, SVIKIS DS, MCGUEM, LYKKEN DT, HESTON LL, CLAYTON PJ: Heterogeneity in the inheritance of alcoholism. Arch. Gen. Psychiatry (1991) 48:19-28.
11. PRESCOTT CA, AGGEN SH, KENDLER KS: Sex differences in the sources of genetic liability to alcohol abuse and dependence in a population-based sample of US twins. Alcohol. Clin. Exp. Res. (1999) 23:1136-1144. • In a US sample of twins, genetic factors play a major role in the development of alcoholism in both women (55 - 66%) and men (51 - 56%).
12. 2 receptor gene in alcoholism. JAMA (1990) 263:2055-2060. •• This paper was the first to show the TaqIA DRD2 A1 allele was associated with severe alcoholism in both men and women.
13. 2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behavior. Pharmacogenetics (1995) 5:121-141.
14. 2 dopamine receptor gene is associated but not linked with alcoholism. JAMA (1991) 266:1833-1834. • An early meta-analysis that showed the TaqIA DRD2 allele was associated significantly with alcoholism.
15. GORWOOD P, ADES J, FEINGOLD J: Are genes coding for dopamine receptors implicated in alcoholism? Eur. Psychiatry (1994) 9:63-69.
16. 2 receptor gene in samples of female and male alcoholics. Am. J. Med. Genet. (1995) 60:267-271.
17. 2 dopamine receptor gene: a review of association studies in alcoholism and phenotypes. Alcohol (1998) 16:33-45.
18. 2 receptor and alcoholism: a meta-analysis. Am. J. Med. Genet. (1993) 48:78-82.
19. 2 receptor gene. Trends Neurosci. (1993) 16:83-88.
20. GURLING HMD, COOK CCH: The genetic predisposition to alcohol dependence. Curr. Opin. Psychiatry (1999) 12:269-275.
21. 2 dopamine receptor gene and alcoholism: a reappraisal. JAMA (1993) 269:1673-1677.
22. 2 receptor gene [letter]. JAMA (1993) 270:1547.
23. 2 receptor gene and alcoholism. JAMA (1990) 264:3156-3160.
24. 2 dopamine receptor locus. Arch. Gen. Psychiatry (1991) 48:655-663.
25. 2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA (1991) 266:1793-1800.
26. 2 dopamine receptor gene (DRD2) and alcoholism. JAMA (1991) 266:1801-1807.
27. 2 dopamine receptor gene with severe alcoholism. Alcohol (1991) 8:409-416.
28. 2 receptor gene. Alcohol. Clin. Exp. Res. (1992) 16:806-809.
29. 2 dopamine receptor genotype and cerebral spinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States. Acta Psychiatr. Scand. (1992) 86:351-357.
30. 2 dopamine receptor gene and alcoholism. J. Psychiatr. Res. (1993) 27:173-179.
31. 2 dopamine receptor locus (DRD2) in alcoholics and controls. Genomics (1994) 19:12-20.
32. NOBLE EP, SYNDULKO K, FITCH RJ et al.: TaqI A alleles in medically ill alcoholic and nonalcoholic patients. Alcohol Alcohol. (1994) 29:729-744.
33. 2 receptor gene polymorphisms in Scandinavian chronic alcoholics. Eur. Arch. Psychiatry Clin. Neursci. (1994) 244:26-32.
34. 2 (TaqI A) receptor gene polymorphisms with reduced dopaminergic sensitivity in alcoholism. Alcohol. Clin. Exp. Res. (1996) 20:1109-1113.
35. 2 dopamine receptor A1 allele with alcoholism: medical severity of alcoholism and type of controls. Biol. Psychiatry (1997) 41:386-393. • This study shows the frequency of the TaqIA DRD2 A1 allele progressively decreases in controls that include subjects with a negative family history of alcoholism (FH-), controls without previous hazardous alcohol consumption (PHAC), and controls with both FH- and PHAC. Conversely, the frequency of the TaqIA DRD2 A1 allele progressively increases in alcoholics as the severity of their disorder increases.
36. 1 dopamine receptor gene and alcoholism in Finland. Psychiatr. Genet. (1997) 7:19-25.
37. 4 receptor genes and Slavic-surnamed alcoholic patients. Addict. Biol. (1999) 4:399-404.
38. BABOR TF, HOFMANN M, DEL BOCA FK et al.: Types of alcoholics: I. Evidence for an empirically derived typology based on indicators of vulnerability and severity. Arch. Gen. Psychiatry (1992) 49:599-608.
39. CLONINGER CR: Neurogenetic adaptive mechanisms in alcoholism. Science (1987) 236:410-416. • 3D model of personality based on three neurotransmitter systems: novelty seeking (dopamine), harm avoidance (serotonin) and reward dependence (noradrenaline).
40. 2 dopamine receptor gene and severe alcoholism. Biol. Psychiatry (1992) 31:285-290.
41. 2 receptor gene is located on chromosome 11 at q22-q23 and identifies a Taq1 RFLP. Am. J. Hum. Genet. (1989) 45:778-785. • Identifies a region of chromosome 11 that harbours the DRD2 gene.
42. 2 receptor TaqI B RFLP is more frequent in polysubstance abusers. Arch. Gen. Psychiatry (1992) 49:723-727.
43. REGIER DA, FARMER ME, RAE DS et al.: Comorbidity of mental disorders with alcohol and other drug abuse. JAMA (1990) 264:2511-2518.
44. ROBINS LN, HELZER JE, PRZYBECK TR, REGIER DA: Alcohol disorders in the community: a report from the epidemiologic catchment area. In: Alcoholism: Origins and Outcome. Rose RM, Barrett J (Eds.), Raven Press, New York, USA (1988):15-29.
45. 2 dopamine receptor in alcohol consumption, dependence and chronology of use in alcohol dependent patients. (2000) (Submitted).
46. SKINNER HA, HORN JL: Alcohol Dependence Scale (ADS): Users Guide. Addiction Research Institutes, Toronto (1984).
47. GANDELMAN KY, HARMON S, TODD RD, O'MALLEY KL: Analysis of the structure and expression of the human dopamine D2A receptor gene. J. Neurochem. (1991) 56:1024-1029.
48. 2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23. Genomics (1992) 14:1010-1018.
49. 2 dopamine receptor TaqI B RFLP in severe alcoholics. Alcohol (1993) 10:59-67.
50. 2 receptor gene in alcoholism or schizophrenia. Analysis using denaturing gradient gel electrophoresis. JAMA (1994) 271:204-208.
51. NOBLE EP, ZHANG X, RITCHIE TL, SPARKES RS: Haplotypes at the DRD2 locus and severe alcoholism. Am. J. Med. Genet. (2000) in press. • Three intronic sites of the DRD2 gene were found to be strongly associated with severe alcoholism.
52. HILL SY: Alternative strategies for uncovering genes contributing to alcoholism risk: unpredictable findings in a genetic wonderland. Alcohol (1998) 16:53-59.
53. 4 receptor genes and alcoholism. Am. J. Med. Genet. (1999) 88:676-685. • Using a non-parametric technique (SIBPAL) in a sample of high-density alcoholic families, linkage was observed when the more severe alcoholics were compared to the non-alcoholic controls.
54. 2 dopamine receptor locus in heavy drinking and alcoholism. Br. J. Psychiatry (1996) 169:243-248.
55. 2 dopamine receptor locus in heavy drinking and alcoholism. Psychiatric Genet. (1993) 3:130. • This is the first report of a genetic linkage of the DRD2 gene with alcohol problems.
56. 2 receptor (DRD2) with alcoholism. Alcohol. Clin. Exp. Res. (1998) 22:505-512.
57. CURTIS D, ZHAO JH, SHAM PC: Comparison of GENEHUNTER and MFLINK for analysis of COGA linkage data. Genet. Epidemiol. (1999) 17(Suppl. 1):S115-S120.
58. KRUGLYAK L, LANDER ES: Faster multipoint linkage analysis using Fourier transforms. J. Comp. Biol. (1998) 5:1-7.
59. CURTIS D, SHAM PC: Model-free linkage analysis using likelihoods. Am. J. Hum. Genet. (1995) 57:703-716.
60. WALDMAN ID, ROBINSON BF, RHEE SH: A logistic regression extension of the transmission disequilibrium test for continuous traits: application to linkage disequilibrium between alcoholism and the candidate genes DRD2 and ADH3. Genet. Epidemiol. (1999) 17(Suppl. 1):S379-S384.
61. WISE RA, ROMPRE PP: Brain dopamine and reward. Ann. Rev. Psychol. (1989) 40:191-225.
62. KOOB GR: Drugs of abuse. Anatomy, pharmacology and function of reward pathways. Trends Pharmacol. Sci. (1992) 13:177-184.
63. 2 receptor RFLPs, haplotypes and their association with substance use in black and Caucasian research volunteers. Hum. Hered. (1993) 43:209-218.
64. 2 receptor gene: a genetic risk factor in substance abuse. Drug Alcohol Depend. (1994) 34:175-180.
65. 2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend. (1993) 33:271-285.
66. 2 dopamine receptor gene TaqI A1 and B1 restriction fragment length polymorphisms: enhanced frequencies in psychostimulant-preferring polysubstance abusers. Biol. Psychiatry (1996) 40:776-784.
67. 2 dopamine receptor gene and cigarette smoking: a reward gene? Med. Hypotheses (1994) 42:257-260.
68. 2 receptor (DRD2) gene: a genetic risk factor in smoking. Pharmacogenetics (1996) 6:73-79.
69. 2 dopamine receptor gene and smoking status in lung cancer patients. J. Natl. Cancer Inst. (1998) 90:358-363.
70. LERMAN C, CAPORASO NE, AUDRAIN J et al.: Evidence suggesting the role of specific genetic factors in cigarette smoking. Health Psychol. (1999) 18:14-20.
71. NOBLE EP: The DRD2 gene, smoking and lung cancer. J. Natl. Cancer Inst. (1998) 90:343-345.
72. 2 dopamine receptor A1 allele and opioid dependence: association with heroin use and response to methadone treatment. Am. J. Med. Genet. (In Press). • The TaqIA DRD2 A1 allele was found to be associated with opioid dependence. Moreover, those who failed a methadone treatment programme had four times higher frequency of the A1 allele than those who succeeded.
73. 2 receptor (DRD2) as a major gene in obesity and height Biochem. Med. Metabolic Biol. (1993) 50:176-185.
74. 2 dopamine receptor gene and obesity. Int. J. Eating Dis. (1994) 15:205-217.
75. 2 receptor (DRD2) gene. Mol. Psychiatry (1996) 1:325-335.
76. BLUM K, BRAVERMAN ER, WOOD RC et al.: Increased prevalence of the TaqI A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorders: a preliminary report. Pharmacogenetics (1996) 6:297-305.
77. 2 dopamine receptor gene and obesity. Nutr. Res. (2000) 20:371-380.
78. PEREZ DE CASTRO I, SANTOS J, TORRES P et al.: A weak association between TH and DRD2 genes and bipolar affective disorder in a Spanish sample. J. Med. Genet. (1995) 32:131-134.
79. SOUERY D, LIPP O, MAHIEU B et al.: Association study of bipolar disorder with candidate genes involved in catecholamine neurotransmission: DRD2, DRD3, DAT1 and TH genes. Am.J.Med. Genet. (1996) 67:551-555.
80. 2 receptor genes and bipolar affective disorder. Am. J. Psychiatry (1992) 149:199-201.
81. 2 receptor variant S311C in schizophrenia and affective disorders. Am. J. Med. Genet. (1996) 67:133-138.
82. 2 receptor gene. Psychiatr. Genet. (1995) 5:63-65.
83. 4 receptor and transporter gene polymorphisms and mood disorders. J. Affect. Disord. (1996) 40:7-13.
84. 2 receptor gene: lack of association with schizophrenia and bipolar affective disorder. J. Neural Transm. (1998) 105:101-109.
85. 2 receptor promoter region with bipolar affective disorder or unipolar affective disorder. Am. J. Med. Genet. (1998) 81:385-387.
86. HO LW, FURLONG RA, RUBINSZTEIN JS, WALSH C, PAYKEL ES, RUBINSZTEIN DC: Genetic associations with clinical characteristics in bipolar affective disorder and recurrent unipolar depressive disorder. Am. J. Med. Genet. (2000) 96:36-42.
87. SEEMAN P: Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse (1987) 1:133-152.
88. 2 receptor molecular variant with schizophrenia. Lancet (1994) 343:703-704.
89. 311 polymorphism in schizophrenia. Lancet (1994) 343:1045-1046.
90. 311 variant associated with disorganized symptomatology of schizophrenia. Schizophr. Res. (1998) 34:207-210.
91. 2 receptor gene is associated with schizophrenia. Hum. Mol. Genet. (1997) 6:577-582.
92. 2 receptor gene and schizophrenia. Schizophr. Res. (1999) 40:31-36.
93. BREEN G, BROWN J, MAUDE S et al.: ·141C Del/Ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population. Am. J. Med. Genet. (1999) 88:407-410.
94. 2 receptor gene and schizophrenia in Japanese subjects: replication and evaluation for antipsychotic features. Int. J. Neuropharmacol. (1999) 2:181-186.
95. 2 receptors with schizophrenic and affective disorders. Zh. Neuropatol. Psikbiatr. Im. S. S. Korsakova (1998) 98:32-35.
96. SOBELL J, SIGURDSON D, HESTON L, SOMMER S: S311C D2DR variant: no association with schizophrenia. Lancet (1994) 344:621-622.
97. 311 is not associated with chronic schizophrenia. Am. J. Med. Genet. (1996) 67:483-484.
98. 2 receptor gene (DRD2) and drug response: association studies. Schizophr. Res. (1998) 29:127.
99. TALLERICO T, ULPIAN C, LIU ISC: Dopamine D-2 receptor promoter polymorphism: no association with schizophrenia. Psychiatry Res. (1999) 85:215-219.
100. 311 DRD2 molecular variant with schizophrenia using a classical case control study and the haplotype relative risk. Schizophr. Res. (1997) 25:117-121.
101. 2 receptor gene Cys 311 variant and schizophrenia. Am.J.Med. Genet. (1996) 67:208-211.
102. COMINGS DE: Tourette Syndrome and Human Behavior. Hope Press, Duarte, CA, USA (1990):1-828.
103. COMINGS DE, WU S, CHIU C et al.: Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes - DRD2, DβH and DAT1. Am. J. Med. Genet. (1996) 67:264-288. • The authors suggest that TS, attention deficit hyperactivity, stuttering, oppositional defiant and conduct disorder and other behaviours associated with TS are due to the contribution of variants of three dopaminergic genes: DRD2, DβH and DAT1.
104. 2 receptor (DRD2) and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB). Mol. Psychiatry (1997) 2:239-246.
105. 2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: a study and replication. Biol. Psychiatry (1996) 40:368-372.
106. 2 receptor gene in pathological gambling. Pharmacogenetics (1996) 6:223-234.
107. 4 receptor gene polymorphisms. Am. J. Med. Genet. (1994) 54:361-364.
108. 2 intronic polymorphism in patients with Parkinson's disease. Neurosci. Lett. (1999) 273:151-154.
109. PLANTÉ-BORDENEUVE V, TAUSSIG D, THOMAS F et al.: Evaluation of four candidate genes encoding proteins of the dopamine pathway in familial and sporadic Parkinson's disease: evidence for association of a DRD2 allele. Neurology (1997) 48:1589-1593.
110. 2 receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD. Neurology (1999) 53:1425-1430.
111. 2 receptor gene is a susceptibility locus for Parkinson's disease. Mov. Disord. (2000) 15:127-131.
112. MAKOFF AJ, GRAHAM JM, ARRANZ MJ et al.: Association study of dopamine receptor gene polymorphisms with drug-induced hallucinations in patients with idiopathic Parkinson's disease. Pharmacogenetics (2000) 10:43-48.
113. 2 receptor gene and tardive dyskinesia in schizophrenia. Biol. Psychiatry (1997) 41:827-829.
114. 2 dopamine receptor with myoclonus dystonia. Proc. Natl. Acad. Sci. USA (1999) 96:5173-5176.
115. PEROUTKA SJ: Dopamine and migraine. Neurology (1997) 49:650-656.
116. 2 receptor (DRD2) NcoI alleles. Neurology (1997) 49:201-206.
117. 2 receptor (DRD2) NcoI alleles. Mol. Medicine (1998) 4:14-21.
118. DEL ZOMPO M, CHERCHI A, PALMAS MA et al.: Association between dopamine receptor genes and migraine without aura in a Sardinian sample. Neurology (1998) 51:781-786.
119. 2 dopamine receptors.
120. 2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics (1997) 7:479-484.
121. 2 receptor availability in healthy volunteers. Mol. Psychiatry (1998) 3:256-260.
122. 2 receptor gene. Mol. Psychiatry (1998) 3:261-265.
123. 2 dopamine receptor expression. Mol. Psychiatry (1998) 3:198-203.
124. 2 dopamine receptors in healthy subjects with the TaqIA DRD2 A1, B1 and promoter allele.
125. 2 dopamine receptor polymorphism. Brain Res. (1996) 718:193-197.
126. 2 dopamine receptor gene in children with idiopathic short stature. J. Hum. Genet. (1999) 44:26-29. • A significantly higher frequency of the TaqIA DRD2 A1 allele was found in short compared to normal stature subjects. Within subjects of short stature, those with the A1 allele had reduced bone age to chronological age ratio, reduced IGF-1 and reduced GH secretion than those without this allele.
127. 2 receptor gene to heritability of stature: linkage and association studies. Ann. Hum. Genet. (1999) 63:147-151.
128. 11C-glucose. Acta Psychiatr. Scand. (1988) 78:234-241.
129. ADAMS KM, GILMAN S, KOEPPE RA et al.: Neuropsychological deficits are correlated with frontal hypometabolism in positron emission tomography studies of older alcoholic patients. Alcohol. Clin. Exp. Res. (1993) 17:205-210.
130. 2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse (1993) 14:169-177.
131. VOLKOW ND, HITZEMANN R, WANG G-J et al.: Long-term frontal brain metabolism changes in cocaine abusers. Synapse (1992) 11:184-190.
132. 18F]deoxyglucose showed reduced glucose metabolism in healthy subjects with the TaqIA DRD2 A1 allele in a number of dopamine receptor rich areas of the brain.
133. 2 dopamine receptor A1 allele. Am. J. Hum. Genet. (1994) 54:658-668.
134. 2 dopamine receptor A1 allele. Pharmacogenetics (1994) 3:313-322.
135. 2 dopamine receptor Taq1 A genotypic differences in event-related brain potentials. In: Problems of Drug Dependence, 1995. NIDA Research Monograph 162. Harris LS (Ed.), National Institute of Drug Abuse, Rockville, MD, USA (1996):129.
136. HILL SY, LOCKE J, ZEZZA N et al.: Genetic association between reduced P300 amplitude and the DRD2 dopamine receptor A1 allele in children at high-risk for alcoholism. Biol. Psychiatry (1998) 43:40-51. • Children with the TaqIA DRD2 A1 allele have reduced amplitude of the P300, a late positive component of the event-related potential.
137. 2 dopamine receptor A1 allele. Behav. Genet. (1995) 25:45-58. • Children with the TaqIA DRD2 A1 allele have reduced visuospatial performance measured by Benton's Judgement of Line Orientation Test.
138. 2 dopamine receptor (DRD2) gene and family stress. Interactive effects on cognitive functioning in children. Behav. Genet. (1997) 27:33-43.
139. 4 receptor (DRD4) exon III polymorphism associated with the human personality trait of novelty seeking. Nature Genet. (1996) 12:78-80. • Variants of the DRD4 gene influence novelty seeking scores.
140. 4 dopamine receptor gene and measures of novelty seeking. Nature Genet. (1996) 12:81-84. • Variants of the DRD4 gene influence novelty seeking scores.
141. 4 receptor (DRD4) 16 amino acid repeat polymorphism and novelty seeking. Mol. Psychiatry (1996) 1:388-391.
142. 4 receptor gene polymorphism. Am. J. Psychiatry (1997) 154:697-699.
143. 4 dopamine receptor polymorphisms and personality. Am. J. Med. Genet. (1998) 81:257-267. • Variants of the DRD2 and the DRD4 gene each significantly contribute to the personality trait of novelty seeking. However, when variants of these two genes are combined, a stronger contribution is found to novelty seeking.
144. 4): linkage studies in families of alcoholics. Am. J. Med. Genet. (1999) 88:634-641.
145. 2 dopatnine receptor A1 allele. Nature Med. (1995) 1:337-341. •• This study shows the feasibility of a pharmacogenomic approach in the treatment of a certain genetic type of alcoholic.
146. 2 receptor gene TaqI A RFLP in Japanese. Biol. Psychiatry (1993) 33:108-114.
147. KIDD JR, PAKSTIS AJ, KIDD KK: Global levels of DNA variation. Proceedings of the 4th International Symposium on Human Identification. Promega, Madison (1993):21-30.
148. GOLDMAN D: Genetic transmission. In: Recent Developments in Alcoholism (Volume 11). Galanter M (Ed.), Plenum Press, New York, USA (1993):232-248.
149. RISCH N, TENG J: The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases. I. DNA pooling. Genome Res. (1998) 8:1273-1288.
150. NEISWANGER K, KAPLAN BB, HILL SY: What can the DRD2/alcoholism story teach us about association studies in psychiatric genetics. Am. J. Med. Genet. (1995) 60:272-275.
151. COMINGS DE: Why different rules are required for polygenic inheritance: lessons learned from studies of the DRD2 gene. Alcohol (1998) 16:61-70.
152. RISCH N, MERIKANGAS K: The future of genetic studies of complex human diseases. Science (1996) 273:1516-1517. •• The authors argue that linkage analysis, which has been used successfully to find major genes, has limited power to detect genes of modest effects. They suggest that family-based association analysis which utilises candidate genes has far greater power.
153. HODGE SE: What association analysis can and cannot tell us about the genetics of complex disease. Am. J. Med. Genet. (1994) 54:318-323.
154. BLACKWOOD EM, KADONAGA JT: Going the distance: a current view of enhancer action. Science (1998) 28:60-63.
155. FLEISS JL: Statistical Methods for Rates and Proportions. John Wiley and Sons, New York (1981).
156. A receptor β3 subunit genes and alcoholism. Psychiatry Res. (1998) 81:133-147.
157. NOBLE EP: The gene that rewards alcoholism. Sci. Am. Sci. Med. (1996) 3:52-61.