Journal article

Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations

C Liu, CA Bousman, C Pantelis, E Skafidas, D Zhang, W Yue, IP Everall

TRANSLATIONAL PSYCHIATRY | SPRINGERNATURE | Published : 2017

Abstract

Genome-wide association studies have confirmed the polygenic nature of schizophrenia and suggest that there are hundreds or thousands of alleles associated with increased liability for the disorder. However, the generalizability of any one allelic marker of liability is remarkably low and has bred the notion that schizophrenia may be better conceptualized as a pathway(s) disorder. Here, we empirically tested this notion by conducting a pathway-wide association study (PWAS) encompassing 255 experimentally validated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways among 5033 individuals diagnosed with schizophrenia and 5332 unrelated healthy controls across three distinct ethnic populat..

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Grants

Awarded by Brain and Behavior Research Foundation (NARSAD) Young Investigator Award


Awarded by National Key Research and Development Program of China


Awarded by National Key Technology R&D Program of China


Awarded by NHMRC Senior Principal Research Fellowship


Awarded by National Institute of Mental Health


Awarded by NCI\SAIC-Frederick (SAIC-F)


Awarded by Roswell Park Cancer Institute


Awarded by Science Care


Awarded by Laboratory, Data Analysis and Coordinating Center (LDACC)


Awarded by SAIC-F


Awarded by University of Miami


Awarded by University of Geneva


Awarded by University of Chicago


Awarded by University of North Carolina-Chapel Hill


Awarded by Harvard University


Awarded by Stanford University


Awarded by Washington University St. Louis


Awarded by University of Pennsylvania


Awarded by NATIONAL INSTITUTE OF MENTAL HEALTH


Awarded by NATIONAL INSTITUTE ON DRUG ABUSE


Funding Acknowledgements

We acknowledge the financial support of the Brain and Behavior Research Foundation (NARSAD) Young Investigator Award (CAB, Grant# 20526), National Key Research and Development Program of China (2016YFC1307001) and National Key Technology R&D Program of China (2015BAI13B01). CAB was supported by a University of Melbourne Ronald Phillip Griffith Fellowship. CP was supported by a NHMRC Senior Principal Research Fellowship (628386 and 1105825).Funding support for the Genome-Wide Association of Schizophrenia Study was provided by the National Institute of Mental Health (R01 MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01 MH81800, U01 MH46276, U01 MH46289 U01 MH46318, U01 MH79469 and U01 MH79470) and the genotyping of samples was provided through the Genetic Association Information Network (GAIN). The datasets used for the analyses described in this manuscript were obtained from the database of Genotypes and Phenotypes (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000021.v1.p1 and phs000167.v1.p1. Samples and associated phenotype data for the Genome-Wide Association of Schizophrenia Study were provided by the Molecular Genetics of Schizophrenia Collaboration (PI: Pablo V. Gejman, Evanston Northwestern Healthcare (ENH) and Northwestern University, Evanston, IL, USA).The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI\SAIC-Frederick (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171) and Science Care (X10S172). The Laboratory, Data Analysis and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by a supplements to University of Miami grants DA006227 and DA033684 and to contract N01MH000028. Statistical methods development grants were made to the University of Geneva (MH090941 and MH101814), the University of Chicago (MH090951, MH090937, MH101820, MH101825), the University of North Carolina-Chapel Hill (MH090936 and MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St. Louis (MH101810) and the University of Pennsylvania (MH101822). The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 5/12/2016.