Paternal age of schizophrenia probands and endophenotypic differences from unaffected siblings

James Schmeidler, Laura C. Lazzeroni, Neal R. Swerdlow, Rui P. Ferreira, David L. Braff, Monica E. Calkins, Kristin S. Cadenhead, Robert Freedman, Michael F. Green, Tiffany A. Greenwood, Raquel E. Gur, Ruben C. Gur, Gregory A. Light, Ann Olincy, Keith H. Nuechterlein, Allen D. Radant, Larry J. Seidman, Larry J. Siever, William S. Stone, Joyce SprockCatherine A. Sugar, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Jeremy M. Silverman

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

We evaluated the discrepancy of endophenotypic performance between probands with schizophrenia and unaffected siblings by paternal age at proband birth, a possible marker for de novo mutations. Pairs of schizophrenia probands and unaffected siblings (N=220 pairs) were evaluated on 11 neuropsychological or neurophysiological endophenotypes previously identified as heritable. For each endophenotype, the sibling-minus-proband differences were transformed to standardized scores. Then for each pair, the average discrepancy was calculated from its standardized scores. We tested the hypothesis that the discrepancy is associated with paternal age, controlling for the number of endophenotypes shared between proband and his or her sibling, and proband age, which were both associated with paternal age. The non-significant association between the discrepancy and paternal age was in the opposite direction from the hypothesis. Of the 11 endophenotypes only sensori-motor dexterity was significant, but in the opposite direction. Eight other endophenotypes were also in the opposite direction, but not significant. The results did not support the hypothesized association of increased differences between sibling/proband pairs with greater paternal age. A possible explanation is that the identification of heritable endophenotypes was based on samples for which schizophrenia was attributable to inherited rather than de novo/non-inherited causes.

Original languageEnglish
Pages (from-to)67-71
Number of pages5
JournalPsychiatry Research
Volume219
Issue number1
DOIs
StatePublished - 30 Sep 2014
Externally publishedYes

Bibliographical note

Funding Information:
This material is based upon work supported by NIMH grants R01 MH65571 , R01 MH042228 , R01 MH65588 , R01 MH65562 , R01 MH65707 , R01 MH65554 , R01 MH65578 , R01 MH086135 , and R01 MH65558 . We are grateful to all the subjects who participated in this study.

Keywords

  • Copy number variants
  • De novo mutations
  • Familial schizophrenia
  • Genetic risk
  • Sporadic schizophrenia

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