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We read with interest the article on a positive association between a polymorphism in the tryptophan hydroxylase (TPH) gene and manic-depressive illness.¹ The authors found a significantly increased rate of the "A" allele in patients compared with control subjects (52% vs 36%).¹ The TPH gene encodes for the rate-limiting enzyme of serotonin synthesis, making it a strong candidate gene for manic-depressive disorder; therefore, we attempted to replicate these results.

Association studies using the case-control design have the potential to produce false-positive results owing to population stratification, even when careful matching has been performed. An elegant and powerful way of overcoming this problem is to use the parents of probands and to examine whether one allele is preferentially transmitted over the other from parents who are heterozygous (the transmission/disequilibrium test).² We have collected a new sample of such parent-offspring trios and have genotyped them for the polymorphism described in . . . [Full Text of this Article]

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Catechol O-Methyltransferase, Serotonin Transporter, and Tryptophan Hydroxylase Gene Polymorphisms in Bipolar Disorder Patients With and Without Comorbid Panic Disorder
Rotondo et al.
Am. J. Psychiatry 2002;159:23-29.
ABSTRACT | FULL TEXT  

No Allelic Association Between Bipolar Affective Disorder and the Tryptophan Hydroxylase Gene
McQuillin et al.
Arch Gen Psychiatry 1999;56:99-101.
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