No abstract

This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors.

Parents of patients with childhood-onset schizophrenia have a higher rate of schizophrenia spectrum disorders than parents of patients with adult-onset illness. This is consistent with the hypothesis that a childhood onset of schizophrenia is due, at least in part, to a greater familial diathesis for the disorder.

Bipolar affective disorder (BPAD; manicdepressive illness) is characterized by episodes of mania and͞or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score ‫؍‬ 4.05, P ‫؍‬ 5.22 ؋ 10 ؊4 ; SIBPAL P empirical value <3 ؋ 10 ؊5 ) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score ‫؍‬ 3.29, P ‫؍‬ 2.57 ؋ 10 ؊3 ; SIBPAL P empirical value <1 ؋ 10 ؊3 ) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.