Genetic linkage analysis supports the presence of two susceptibility loci for alcoholism and heavy drinking on chromosome 1p22.1-11.2 and 1q21.3-24.2.
BACKGROUND
In order to confirm a previous finding of linkage to alcoholism on chromosome 1 we have carried out a genetic linkage study.


METHODS
DNA from eighteen families, densely affected by alcoholism, was used to genotype a set of polymorphic microsatellite markers at loci approximately 10 centimorgans apart spanning the short arm and part of the long arm of chromosome 1. Linkage analyses were performed using the classical lod score and a model-free method. Three different definitions of affection status were defined, these were 1. Heavy Drinking (HD) where affected subjects drank more than the Royal College of Psychiatrists recommended weekly amount. 2. The Research Diagnostic Criteria for alcoholism (RDCA) 3. Alcohol Dependence Syndrome (ADS) as defined by Edwards and Gross (1976) and now incorporated into ICD10 and DSMIV.


RESULTS
Linkage analyses with the markers D1S1588, D1S2134, D1S1675 covering the cytogenetic region 1p22.1-11.2 all gave positive two point and multipoint lods with a maximum lod of 1.8 at D1S1588 (1p22.1) for the RDCA definition of alcoholism. Another lod of 1.8 was found with D1S1653 in the region 1q21.3-24.2 using the HD affection model.


CONCLUSIONS
These results both support the presence of linkage in the 1p22.1-11.2 region which was previously implicated by the USA Collaborative Study of the Genetics of Alcoholism (COGA) study and also suggest the presence of another susceptibility locus at 1q21.3-24.2.
Guerrini
Irene
I
Molecular Psychiatry Laboratory, Windeyer Institute for Medical Sciences, Department of Mental Health Sciences, Royal Free and University College London Medical School, 46 Cleveland Street, London, W1T 4JF, UK. i.guerrini@ucl.ac.uk <i.guerrini@ucl.ac.uk>
Cook
Christopher C H
CC
Kest
Wendy
W
Devitgh
Audrey
A
McQuillin
Andrew
A
Curtis
David
D
Gurling
Hugh M D
HM
D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D005192:Family Health; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats
J Stud Alcohol. 1982 Nov;43(11):1157-70
7182675
Br Med J. 1976 May 1;1(6017):1058-61
773501
Acta Genet Med Gemellol (Roma). 1984;33(2):333-9
6540966
Hum Hered. 1996 Jul-Aug;46(4):226-35
8807326
Electrophoresis. 1992 Aug;13(8):487-94
1451682
Am J Hum Genet. 2003 Apr;72(4):879-90
12612864
J Stud Alcohol. 1997 Sep;58(5):464-73
9273910
Curr Opin Genet Dev. 1998 Jun;8(3):282-6
9691005
Arch Gen Psychiatry. 1990 Apr;47(4):313-9
2322082
Genet Epidemiol. 1999;17 Suppl 1:S115-20
10597422
Addiction. 2001 Jun;96(6):903-10
11399221
Alcohol Clin Exp Res. 2000 Jul;24(7):933-45
10923994
Genomics. 1995 Dec 10;30(3):450-8
8825630
BMC Genet. 2003;4 Suppl 1:S106
14975174
Alcohol Clin Exp Res. 2002 Oct;26(10):1453-60
12394277
BMJ. 1997 Apr 19;314(7088):1164-8
9146389
Psychopharmacology (Berl). 2002 Apr;160(4):398-407
11919667
Am J Med Genet. 1998 May 8;81(3):216-21
9603607
Br J Psychiatry. 1986 Apr;148:435-41
3730710
Am J Med Genet. 1998 May 8;81(3):207-15
9603606
Br J Addict. 1983 Jun;78(2):145-55
6135435
Addict Biol. 2000 Apr 1;5(2):187-94
20575834
Am J Psychiatry. 2001 May;158(5):718-24
11329392
Am J Hum Genet. 1989 Mar;44(3):397-401
2563634
Psychol Med. 1994 Feb;24(1):69-80
8208896
Am J Hum Genet. 1995 Sep;57(3):703-16
7668300