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Significant correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy

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Abstract

Prior family and adoption studies have suggested a genetic relationship between schizophrenia and schizotypy. However, this has never been verified using linkage methods. We therefore attempted to test for a correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy. The Irish study of high-density schizophrenia families comprises 270 families with at least two members with schizophrenia or poor-outcome schizoaffective disorder (n=637). Non-psychotic relatives were assessed using the structured interview for schizotypy (n=746). A 10-cM multipoint, non-parametric, autosomal genome-wide scan of schizophrenia was performed in Merlin. A scan of a quantitative trait comprising ratings of DSM-III-R criteria for schizotypal personality disorder in non-psychotic relatives was also performed. Schizotypy logarithm of the odds (LOD) scores were regressed onto schizophrenia LOD scores at all loci, with adjustment for spatial autocorrelation. To assess empirical significance, this was also carried out using 1000 null scans of schizotypy. The number of jointly linked loci in the real data was compared to distribution of jointly linked loci in the null scans. No markers were suggestively linked to schizotypy based on strict Lander–Kruglyak criteria. Schizotypy LODs predicted schizophrenia LODs above chance expectation genome wide (empirical P=0.04). Two and four loci yielded nonparametric LOD (NPLs) >1.0 and >0.75, respectively, for both schizophrenia and schizotypy (genome-wide empirical P=0.04 and 0.02, respectively). These results suggest that at least a subset of schizophrenia susceptibility genes also affects schizotypy in non-psychotic relatives. Power may therefore be increased in molecular genetic studies of schizophrenia if they incorporate measures of schizotypy in non-psychotic relatives.

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Acknowledgements

This work was supported by NIH grants MH-41953, MH-52537, MH-45390, MH-65322, and IT-32 MH-20030. AF was supported by an APA/Lilly Psychiatric Research Fellowship and a NARSAD Young Investigator Award. Data collection was conducted under the supervision of S Humphries, M Healy and A Finnerty. Additional interviews were conducted by J Burke, B Murphy, F Duke, R Shinkwin, M Ni Nuallain, F McMahon, J Downing, T Hebron, B Hanratty, E Crowe, M Doherty, J Bray and L Lowry. This project would not have been possible without the cooperation of the families themselves and the staffs of the many psychiatric hospitals and units in Ireland and northern Ireland and their efforts are greatly acknowledged.

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  1. Mental Health Service Line, Washington VA Medical Center, Washington, DC, USA

    A H Fanous

  2. Department of Psychiatry, Georgetown University Medical Center, Washington, DC, USA

    A H Fanous

  3. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

    A H Fanous, M C Neale, C O Gardner, B T Webb, B P Riley & K S Kendler

  4. Department of Human Genetics, Virginia Commonwealth University, Richmond, VA, USA

    M C Neale, B P Riley & K S Kendler

  5. Genes, Cognition, and Psychosis Program, National Institute of Mental Health, NIH, Bethesda, MD, USA

    R E Straub

  6. Queen's University, Belfast, Northern Ireland, UK

    F A O'Neill

  7. Health Research Board, Dublin, Ireland

    D Walsh

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Fanous, A., Neale, M., Gardner, C. et al. Significant correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy. Mol Psychiatry 12, 958–965 (2007). https://doi.org/10.1038/sj.mp.4001996

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