Linkage studies of D2 and D4 receptor genes and alcoholism

Abstract

The purpose of the present study was to evaluate two polymorphisms near the D2 receptor gene (TaqI A RFLP and C microsatellite) and a VNTR for D4. A nonparametric linkage (NPL) technique, SIBPAL, was used to test for the presence or absence of linkage in 54 multiplex alcoholic families. These families had been ascertained through two alcoholic proband siblings in order to increase the density of alcoholic cases within these pedigrees. Phenotypic definitions of alcoholism were manipulated in an effort to determine the impact of severity (signs of physical dependence, early age of onset, presence of antisocial personality disorder) on the likelihood of finding positive evidence for linkage. A regression analysis that simultaneously evaluated the allele sharing identical by descent for Feighner criteria alcoholism in affected, unaffected, and discordant sib pairs (SIBPAL) for two D2 polymorphisms and the D4 polymorphism gave no evidence for linkage. Phenotypes associated with greater alcoholism severity (presence of physical dependence symptoms, earlier onset, or comorbid antisocial personality disorder) revealed some evidence for linkage. The presence of one or more physical dependence symptoms in combination with Feighner criteria alcoholism provided some evidence favoring linkage (TaqI A and D4). Alcoholics with an earlier onset of alcoholism showed some evidence for linkage especially when the presence of physical dependence was required (e. g., morning drinking, wanted to stop drinking but could not, binges or benders, and evidence of withdrawal symptoms). Finally, alcoholics with antisocial personality disorder differed significantly in their allele sharing from nonalcoholics for both D2 polymorphisms. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:676-685, 1999.

A genome wide search for alcoholism susceptibility genes

“…Two studies have found evidence for linkage in a region containing the D4 receptor polymorphism [Long et al, 1998;Hill et al, 1999a]. Long et al reported a LOD score of 2.11, P = 0.00007 for D11S1984.…”

Between- and Within-Family Association Test of the Dopamine Receptor D2 TaqIA Polymorphism and Alcohol Abuse and Dependence in a General Population Sample of Adults

“…Similar findings were reported from four previous studies of affected family-based samples (Bolos et al, 1990;Edenberg et al, 1998;Neiswanger et al, 1995;Parsian et al, 1991). Increased rates of allele sharing for the TaqI polymorphism have, however, been reported from two sibpair linkage studies (Cook et al, 1996;Hill et al, 1999), although this findings was not replicated in another study . Taken together, our results are congruent with the notion that the A1 allele is not a generalized risk factor for alcohol abuse and dependence symptoms in the general population.…”

Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

“…Our most recent PubMed search found > 3400 published reports on the subject. The A1 allele of the DRD2 gene, Taq1 A1 allele, may also be involved in comorbid antisocial personality disorder symptoms, 52 high novelty seeking, 53–56 alcoholism, 37 and addictive behaviors. 20,33 Addictions are increasingly recognized as sharing a common neuroanatomy and neurobiology.…”