Population-based association analyses of the HOPA(12bp) polymorphism for schizophrenia and hypothyroidism

HOPA is an Xq13 chromosome gene that codes for a RXR nuclear receptor co-ac tivator. In a prior study of the genetic basis of schizophrenia, we showed that exonic polymorphisms in HOPA were associated with increased risk of sc hizophrenia and hypothyroidism in a large cohort of probands from New York, In an attempt to replicate these findings, we examined this relationship i n a cohort of 173 schizophrenic probands (128 males and 45 females providin g 218 alleles) from Iowa. Consistent with the prior findings, we found an i ncreased rate of the HOPA(12bp) exonic polymorphism in schizophrenic proban ds compared with random newborn controls (9 of 218 alleles vs. 33 of 2,049 alleles, P < 0.02). Furthermore, retrospective review of the medical record s showed that two of the nine probands possessing the HOPA(12bp) allele in whom thyroid function was assessed were hypothyroid compared with 6 of 164 probands possessing the normal HOPA(wild) allele(s) (P < 0.06). We conclude that the HOPA(12bp) polymorphism shows a nominally significant association with schizophrenia and a nominal trend for association with hypothyroidism in our study and that further studies are required to define the features of this syndrome and the molecular mechanisms of disease pathogenesis. Am. J. Med, Genet. (Neuropsychiatr. Genet.) 105:130-134, 2001. (C) 2001 Wiley-L iss, Inc.