Association between PRODH and schizophrenia is not confirmed

SIR – It has recently been reported that genetic variants of proline dehydrogenase (PRODH) increase susceptibility to schizophrenia.1 This is of interest since PRODH maps within the

velo-cardio-facial syndrome (VCFS) region of 22q11, deletion of which is one of the strongest known risk factors for schizophrenia.2 We have examined this claim using two samples each with

high power (>99%) to detect the effects reported. Our data suggest that genetic variation at PRODH is unlikely to be associated with even modestly increased risk of schizophrenia, and that

the earlier report is the result of chance.

Liu et al1 reported association between various permutations of SNPs and haplotypes constructed from markers at positions 1766, 1945, and 2026 of PRODH in a small sample (n=107) of

European-American schizophrenic proband–parent trios, in a second sample of 26 trios where the proband had a childhood onset illness, and in a third small sample of 109 adult Afrikaners and

75 controls. Their analysis suggested an association between schizophrenia and a ‘221’ haplotype at three loci 1766/1945/2026, defined by alleles G, T, and C, respectively, and this effect

was strongest for disease of early onset.

Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland

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