Schizophrenia and birthplace of paternal and maternal grandfather in the Jerusalem perinatal cohort prospective study

S. Harlap*, M. C. Perrin, L. Deutsch, K. Kleinhaus, S. Fennig, D. Nahon, A. Teitelbaum, Y. Friedlander, D. Malaspina

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Some forms of epigenetic abnormalities transmitted to offspring are manifested in differences in disease incidence that depend on parent-of-origin. To explore whether such phenomena might operate in schizophrenia spectrum disorders, we estimated the relative incidence of these conditions in relation to parent-of-origin by considering the two grandfathers' countries of birth. In a prospective cohort of 88,829 offspring, born in Jerusalem in 1964-76 we identified 637 cases through Israel's psychiatric registry. Relative risks (RR) were estimated for paternal and maternal grandfathers' countries of birth using proportional hazards methods, controlling for parents' ages, low social class and duration of marriage. After adjusting for multiple observations, we found no significant differences between descendants of maternal or paternal grandfathers born in Iraq, Iran, Turkey, Syria, Yemen, Morocco, Algeria, Tunisia, Libya/Egypt, Poland, USSR, Czechoslovakia, Germany or the USA. Those with paternal grandfathers from Romania (RR = 1.9, 95% CI = 1.3-2.8) or Hungary (1.6, 1.0-2.6) showed an increased incidence; however, those with maternal grandfathers from these countries experienced reduced incidence (RR = 0.5, 0.3-0.8 and 0.4, 0.2-0.8). In post-hoc analyses we found that results were similar whether the comparison groups were restricted to descendants of other Europeans or included those from Western Asia and North Africa; and effects of paternal grandfathers from Romania/Hungary were more pronounced in females, while effects of maternal grandfathers from these countries were similar in males and females. These post-hoc "hypothesis-generating" findings lead one to question whether some families with ancestors in Romania or Hungary might carry a variant or mutation at a parentally imprinted locus that is altering susceptibility to schizophrenia. Such a locus, if it exists, might involve the X chromosome.

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalSchizophrenia Research
Issue number1-3
StatePublished - Jun 2009
Externally publishedYes


FundersFunder number
National Institutes of Health
National Institute of Mental Health2R01 CA080197, R01MH059114, 2K24 MH01699


    • Cohort studies
    • Grandfathers
    • Incidence
    • Jews
    • Maternal
    • Paternal
    • Relative risk
    • Schizophrenia


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