Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia

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Abstract

Phenotypic heterogeneity is a major barrier to understanding the genetic architecture underlying schizophrenia. Incorporating endophenotypes is one way to reduce heterogeneity and facilitate more powerful genetic analysis. Candidate endophenotypes require systematic assessment against endophenotype criteria, and a ranking of their potential utility for genetic analysis. In this study we assess 20 cognitive and personality measures in a sample of 127 families with at least 2 cases of schizophrenia per family (n = 535) plus a set of 30 control families (n = 121) against 4 endophenotype criteria: (a) be associated with the illness but not be a part of its diagnosis, (b) be heritable, (c) co-segregate with the illness in families, and (d) be found in unaffected relatives at a higher rate than in the general population. The endophenotype ranking score (endophenotype ranking variable [ERV]) was used to rank candidate endophenotypes based on their heritability and genetic correlation with schizophrenia. Finally, we used factor analysis to explore latent factors underlying the cognitive and personality measures. Evidence for personality measures as endophenotypes was at least equivalent to that of the cognitive measures. Factor analysis indicated that personality and cognitive traits contribute to independent latent dimensions. The results suggest for this first time that a number of cognitive and personality measures are independent and informative endophenotypes. Use of these endophenotypes in genetic studies will likely improve power and facilitate novel aetiological insights.

Original languageEnglish
Pages (from-to)908-921
Number of pages14
JournalSchizophrenia Bulletin
Volume44
Issue number4
Early online date12 Oct 2017
DOIs
Publication statusPublished - 6 Jun 2018

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title = "Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia",
abstract = "Phenotypic heterogeneity is a major barrier to understanding the genetic architecture underlying schizophrenia. Incorporating endophenotypes is one way to reduce heterogeneity and facilitate more powerful genetic analysis. Candidate endophenotypes require systematic assessment against endophenotype criteria, and a ranking of their potential utility for genetic analysis. In this study we assess 20 cognitive and personality measures in a sample of 127 families with at least 2 cases of schizophrenia per family (n = 535) plus a set of 30 control families (n = 121) against 4 endophenotype criteria: (a) be associated with the illness but not be a part of its diagnosis, (b) be heritable, (c) co-segregate with the illness in families, and (d) be found in unaffected relatives at a higher rate than in the general population. The endophenotype ranking score (endophenotype ranking variable [ERV]) was used to rank candidate endophenotypes based on their heritability and genetic correlation with schizophrenia. Finally, we used factor analysis to explore latent factors underlying the cognitive and personality measures. Evidence for personality measures as endophenotypes was at least equivalent to that of the cognitive measures. Factor analysis indicated that personality and cognitive traits contribute to independent latent dimensions. The results suggest for this first time that a number of cognitive and personality measures are independent and informative endophenotypes. Use of these endophenotypes in genetic studies will likely improve power and facilitate novel aetiological insights.",
keywords = "Journal Article",
author = "McCarthy, {Nina S} and Badcock, {Johanna C} and Clark, {Melanie L} and Knowles, {Emma E M} and Gemma Cadby and Melton, {Phillip E} and Morgan, {Vera A} and John Blangero and Moses, {Eric K} and Glahn, {David C} and Assen Jablensky",
note = "{\circledC} The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.",
year = "2018",
month = "6",
day = "6",
doi = "10.1093/schbul/sbx141",
language = "English",
volume = "44",
pages = "908--921",
journal = "Schizophrenia Bulletin",
issn = "0586-7614",
publisher = "OXFORD UNIV PRESS UNITED KINGDOM",
number = "4",

}