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A Tryptophan Hydroxylase Gene Marker for Suicidality and Alcoholism
David A. Nielsen, PhD;
Matti Virkkunen, MD;
Jaakko Lappalainen, MD;
Monica Eggert, MD;
Gerald L. Brown, MD;
Jeffrey C. Long, PhD;
David Goldman, MD;
Markku Linnoila, MD, PhD
Arch Gen Psychiatry. 1998;55:593-602.
Background Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Low turnover rate of this monoamine neurotransmitter is associated with impaired impulse control. We previously reported that, in Finns, TPH genotype was associated with suicidality, a pathophysiological mechanism that may involve impaired impulse control.
Methods Association and sib-pair linkage analyses of a polymorphism in intron 7 of the TPH gene with suicidality, alcoholism, and the Karolinska Scales of Personality were conducted in 804 Finnish alcoholic offenders, controls, and their relatives, in a sample that included 369 sib pairs.
Results The association of the TPH I7779C (L) allele to suicidality in impulsive offenders reported previously was replicated in a new group of Finnish offenders (P=.001, n=122). The intron 7 variant in the TPH gene showed significant evidence for linkage to suicidality (P=.006 in unaffected sib pairs), severe suicide attempts (P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002).
Conclusions The status of the TPH A779C allele as a marker for suicidality was replicated and linkage with alcoholism and Karolinska Scales of Personality socialization score was also observed. A functional variant(s) in or close to the TPH gene may predispose individuals to suicidality and other behaviors thought to be influenced by serotonin.
From the Section of Molecular Genetics (Dr Nielsen), Laboratory of Neurogenetics (Drs Lappalainen, Long, and Goldman), and Division of Intramural Clinical and Biologic Research (Drs Brown and Linnoila), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Md; and the Department of Psychiatry, University of Helsinki, Helsinki, Finland (Drs Virkkunen and Eggert).
Dr Linnoila is deceased.
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