A recent paper in this Journal reported evidence for the involvement of a novel imprinted gene on chromosome 2p12, the leucine-rich repeat transmembrane neuronal 1 (LRRTM1) gene, in the development of schizophrenia/schizoaffective disorder and human handedness. Francks et al.¹ found a three-marker haplotype upstream of LRRTM1 to be associated with schizophrenia when inherited paternally. It is interesting that the same haplotype was also found to be paternally associated with handedness in a sample of reading-disabled sibships, implying the existence of specific imprinting effects on human brain asymmetry. We tested Francks et al.'s hypotheses in large independent samples of (i) schizophrenia and (ii) dyslexia patients with handedness information.

We genotyped the three markers that define the paternally overtransmitted haplotype in the Francks et al. study, rs1446109–rs1007371–rs723524, in 180 parent–offspring trios with schizophrenia. Assuming the hypothesis that true parent-of-origin effects detected in trios should also result in allelic association in case–control studies,¹ we additionally genotyped these markers in 673 patients with schizophrenia (358 males/315 females) and 1060 controls (566 males/494 females). Individuals, who were recruited from consecutive admissions to the Department of Psychiatry at the University of Bonn, Germany, were of German descent, and had given written informed consent to participate in this study. Diagnoses were made according to Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria² on the basis of a Structured Clinical Interview for DSM-Disorders (SCID-I) interview,³ review of medical records and use of the family history method. The Operational Criteria for Psychotic and Affective Illness (OPCRIT) system was also used.⁴ Genotyping on DNA samples was carried out using Sequenom's iPlex assay (Sequenom Inc., San Diego, CA, USA), according to the manufacturer's protocol.

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