We have attempted to replicate recently published results showing an association between the "A" allele of a restriction fragment length polymorphism in intron 7 of the tryptophan hydroxylase (TPH) gene and manic-depressive illness.1 Polymorphisms in this gene have also been found to be associated with suicidal behavior in depressed patients.2 The TPH gene is the rate-limiting enzyme in the serotonin biosynthetic pathway3 and is localized on the short arm of chromosome 11, which is a region at which we have reported positive lod scores in a genetic linkage analysis of 23 multiply affected bipolar and unipolar affective disorder families.4 We used a case-control design and studied 279 bipolar cases and 315 controls who were selected for having English, Irish, Welsh, or Scottish ancestry. Allele freqencies were very similar to previously published rates in European populations and were also very similar in the bipolar and control groups (0.39 vs 0.41). We conclude that it is unlikely that this polymorphism has any major effect on susceptibility to bipolar affective disorder, at least in the population we have studied.
McQuillin A, Lawrence J, Kalsi G, Chen A, Gurling H, Curtis D. No Allelic Association Between Bipolar Affective Disorder and the Tryptophan Hydroxylase Gene. Arch Gen Psychiatry. 1999;56(1):99-100. doi: