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

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...

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Main Authors: McCarthy, N., Badcock, J., Clark, M., Knowles, E., Cadby, G., Melton, Phillip, Morgan, V., Blangero, J., Moses, E., Glahn, D., Jablensky, A.
Format: Journal Article
Published: Oxford Journals in Association with The Maryland Psychiatric Research Centre 2017
Online Access:http://hdl.handle.net/20.500.11937/58096
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author McCarthy, N.
Badcock, J.
Clark, M.
Knowles, E.
Cadby, G.
Melton, Phillip
Morgan, V.
Blangero, J.
Moses, E.
Glahn, D.
Jablensky, A.
author_facet McCarthy, N.
Badcock, J.
Clark, M.
Knowles, E.
Cadby, G.
Melton, Phillip
Morgan, V.
Blangero, J.
Moses, E.
Glahn, D.
Jablensky, A.
author_sort McCarthy, N.
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-580962017-11-20T08:58:24Z Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia. McCarthy, N. Badcock, J. Clark, M. Knowles, E. Cadby, G. Melton, Phillip Morgan, V. Blangero, J. Moses, E. Glahn, D. Jablensky, A. 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/58096 10.1093/schbul/sbx141 Oxford Journals in Association with The Maryland Psychiatric Research Centre restricted
spellingShingle McCarthy, N.
Badcock, J.
Clark, M.
Knowles, E.
Cadby, G.
Melton, Phillip
Morgan, V.
Blangero, J.
Moses, E.
Glahn, D.
Jablensky, A.
Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia.
title Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia.
title_full Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia.
title_fullStr Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia.
title_full_unstemmed Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia.
title_short Assessment of Cognition and Personality as Potential Endophenotypes in the Western Australian Family Study of Schizophrenia.
title_sort assessment of cognition and personality as potential endophenotypes in the western australian family study of schizophrenia.
url http://hdl.handle.net/20.500.11937/58096