Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations.
BACKGROUND
In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this serotonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism.


METHODS
Linkage was first tested in 640 Finnish subjects, including 166 alcoholic criminal offenders, 261 relatives, and 213 healthy controls. This was followed by a study in a large multigenerational family derived from a Southwestern American Indian tribe (n=418) with a high rate of alcoholism. All subjects were psychiatrically interviewed, blind-rated for psychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects.


RESULTS
In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to HTR1B G861C (P=.04) and weak evidence with D6S284 (P=.06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher HTR1B-861C allele frequency than the other 457 Finns we studied (P=.005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to HTR1B G861C (P=.01) was again observed, and there was also significant linkage to D6S284 (P=.01).


CONCLUSIONS
These results suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15.
Lappalainen
J
J
Section of Population Genetics and Linkage, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20852, USA.
Long
J C
JC
Eggert
M
M
Ozaki
N
N
Robin
R W
RW
Brown
G L
GL
Naukkarinen
H
H
Virkkunen
M
M
Linnoila
M
M
Goldman
D
D
D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D000818:Animals; D000987:Antisocial Personality Disorder / Q000453:epidemiology / Q000235:genetics*; D001483:Base Sequence; D015897:Comorbidity; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology / Q000208:ethnology; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000235:genetics*; D015206:Southwestern United States / Q000453:epidemiology; D020080:Tandem Repeat Sequences / Q000235:genetics
C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin