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Revisiting schizophrenia linkage data in the NIMH Repository: reanalysis of regularized data across multiple studies.

ABSTRACT: The Combined Analysis of Psychiatric Studies (CAPS) project conducted extensive review and regularization across studies of all schizophrenia linkage data available as of 2011 from the National Institute of Mental Health-funded Center for Collaborative Genomic Studies on Mental Disorders, also known as the Human Genetics Initiative (HGI). The authors reanalyzed the data using statistical methods tailored to accumulation of evidence across multiple, potentially highly heterogeneous, sets of data.Data were subdivided based on contributing study, major population group, and presence or absence within families of schizophrenia with a substantial affective component. The posterior probability of linkage (PPL) statistical framework was used to sequentially update linkage evidence across these data subsets (omnibus results).While some loci previously implicated using the HGI data were also identified in the present omnibus analysis (2q36.1, 15q23), others were not. Several loci were found that had not previously been reported in the HGI samples but are supported by independent linkage or association studies (3q28, 12q23.1, 11p11.2, Xq26.1). Not surprisingly, differences were seen across population groups. Of particular interest are signals on 11p15.3, 11p11.2, and Xq26.1, for which data from families with a substantial affective component support linkage while data from the remaining families provide evidence against linkage. All three of these loci overlap with loci reported in independent studies of bipolar disorder or mixed bipolar-schizophrenia samples.Public data repositories provide the opportunity to leverage large multisite data sets for studying complex disorders. Analysis with a statistical method specifically designed for such data enables us to extract new information from an existing data resource.

SUBMITTER: Vieland VJ

PROVIDER: S-EPMC4041610 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other

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Revisiting schizophrenia linkage data in the NIMH Repository: reanalysis of regularized data across multiple studies.

Vieland Veronica J VJ Walters Kimberly A KA Lehner Thomas T Azaro Marco M Tobin Kathleen K Huang Yungui Y Brzustowicz Linda M LM

The American journal of psychiatry 20140301 3

<h4>Objective</h4>The Combined Analysis of Psychiatric Studies (CAPS) project conducted extensive review and regularization across studies of all schizophrenia linkage data available as of 2011 from the National Institute of Mental Health-funded Center for Collaborative Genomic Studies on Mental Disorders, also known as the Human Genetics Initiative (HGI). The authors reanalyzed the data using statistical methods tailored to accumulation of evidence across multiple, potentially highly heterogene ...[more]

PMID: 24170318

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Project description:BackgroundIndividuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.AimsTo link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.MethodWe linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.ResultsIndividuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.ConclusionsThis study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.

Dataset Information

Revisiting schizophrenia linkage data in the NIMH Repository: reanalysis of regularized data across multiple studies.

Publications

Revisiting schizophrenia linkage data in the NIMH Repository: reanalysis of regularized data across multiple studies.

Similar Datasets

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