Older paternal age strongly increases the morbidity for schizophrenia in sisters of affected females

Mary Perrin, Susan Harlap, Karine Kleinhaus, Pesach Lichtenberg, Orly Manor, Benjamin Draiman, Shmuel Fennig, Dolores Malaspina

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The effect of a family history of schizophrenia on the risk for this disorder in the offspring has rarely been examined in a prospective population cohort accounting for the sex of the proband and the first-degree relatives, and certainly not with respect to later paternal age. The influence of affected relatives on offspring risk of schizophrenia was estimated using Cox proportional hazards regression in models that accounted for sex, relation of affected first degree relatives and paternal age in the prospective population-based cohort of the Jerusalem Perinatal Schizophrenia Study. Of all first-degree relatives, an affected mother conferred the highest risk to male and female offspring among the cases with paternal age <35 years, however, female offspring of fathers ≥35 years with an affected sister had the highest risk (RR = 8.8; 95% CI = 3.9-19.8). The risk seen between sisters of older fathers was fourfold greater than the risk to sisters of affected females of younger fathers (RR = 2.2, 95% CI 0.7-6.7). The test for interaction was significant (P = 0.03). By contrast, the risk of schizophrenia to brothers of affected males was only doubled between older (RR = 3.3, 95% 1.6-6.6) and younger fathers (RR = 1.6, 95% CI 0.7-3.5). The most striking finding from this study was the very large increase in risk of schizophrenia to sisters of affected females born to older fathers. The authors speculate that the hypothesized paternally expressed genes on the X chromosome might play some role in these observations.

Original languageEnglish
Pages (from-to)1329-1335
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number7
StatePublished - Oct 2010
Externally publishedYes


  • Epigenetics
  • Hereditary
  • Schizophrenia


Dive into the research topics of 'Older paternal age strongly increases the morbidity for schizophrenia in sisters of affected females'. Together they form a unique fingerprint.

Cite this