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Discovering schizophrenia endophenotypes in randomly ascertained pedigrees.

David C Glahn1, Jeff T Williams2, D Reese McKay1

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This summary is machine-generated.

This study introduces a new method to find schizophrenia endophenotypes in families. It identifies specific cognitive and brain traits linked to genetic risk for schizophrenia.

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Area of Science:

  • Psychiatric Genetics
  • Neuroscience
  • Biostatistics

Background:

  • Schizophrenia's genetic basis is complex and not fully understood.
  • Endophenotypes, genetically correlated traits, offer a way to study schizophrenia risk genes.
  • Existing methods are insufficient for identifying schizophrenia risk genes.

Purpose of the Study:

  • To develop and validate an analytic approach for discovering endophenotypes in extended pedigrees.
  • To identify neurocognitive and neuroanatomic endophenotypes for schizophrenia using this novel approach.

Main Methods:

  • A fixed-effects test within a variance component framework was used.
  • Neurocognitive and cortical surface area traits were analyzed in 1606 Mexican-American individuals from extended pedigrees.
  • Individuals with schizophrenia were excluded to avoid confounding by disease state or medication.

Main Results:

  • The study identified three neurocognitive measures (digit-symbol substitution, facial memory, emotion recognition) associated with schizophrenia liability.
  • Six medial temporal and prefrontal cortical surface areas were found to be associated with schizophrenia liability.
  • The approach was effective even with a small number of affected individuals (6).

Conclusions:

  • A novel analytic approach can successfully discover and rank endophenotypes for schizophrenia.
  • This method is applicable to any heritable disease in randomly ascertained pedigrees.