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

doi:10.1038/tp.2017.8

CORC > 北京大学 > 生命科学学院

	Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations
	Liu, C. ; Bousman, C. A. ; Pantelis, C. ; Skafidas, E. ; Zhang, D. ; Yue, W. ; Everall, I. P.
刊名	TRANSLATIONAL PSYCHIATRY
	2017
关键词	ANGIOTENSIN-CONVERTING ENZYME MAJOR DEPRESSIVE DISORDER SONIC-HEDGEHOG UBIQUITIN PROTEASOME CEREBROSPINAL-FLUID GENETIC-ASSOCIATION SIGNALING PATHWAYS POSITIVE SYMPTOMS KININASE-II POLYMORPHISM
DOI	10.1038/tp.2017.8
英文摘要	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 populations; European-American (EA), African-American (AA) and Han Chinese (CH). We identified 103, 74 and 87 pathways associated with schizophrenia liability in the EA, CH and AA populations, respectively. About half of these pathways were uniquely associated with schizophrenia liability in each of the three populations. Five pathways (serotonergic synapse, ubiquitin mediated proteolysis, hedgehog signaling, adipocytokine signaling and renin secretion) were shared across all three populations and the single-nucleotide polymorphism sets representing these five pathways were enriched for single-nucleotide polymorphisms with regulatory function. Our findings provide empirical support for schizophrenia as a pathway disorder and suggest schizophrenia is not only a polygenic but likely also a poly-pathway disorder characterized by both genetic and pathway heterogeneity.; Brain and Behavior Research Foundation (NARSAD) Young Investigator Award [20526]; National Key Research and Development Program of China [2016YFC1307001]; National Key Technology R&D Program of China [2015BAI13B01]; University of Melbourne Ronald Phillip Griffith Fellowship; NHMRC Senior Principal Research Fellowship [628386, 1105825]; 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, U01 MH79470]; Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS; NCI\SAIC-Frederick (SAIC-F) [10XS170]; Roswell Park Cancer Institute [10XS171]; Science Care [X10S172]; Laboratory, Data Analysis and Coordinating Center (LDACC) [HHSN268201000029C]; SAIC-F [10ST1035, HHSN261200800001E]; University of Miami [DA006227, DA033684, N01MH000028]; University of Geneva [MH090941, MH101814]; University of Chicago [MH090951, MH090937, MH101820, MH101825]; University of North Carolina-Chapel Hill [MH090936, MH101819]; Harvard University [MH090948]; Stanford University [MH101782]; Washington University St. Louis [MH101810]; University of Pennsylvania [MH101822]; SCI(E); SSCI; ARTICLE; 7
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/469372]
专题	生命科学学院
推荐引用方式 GB/T 7714	Liu, C.,Bousman, C. A.,Pantelis, C.,et al. Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations[J]. TRANSLATIONAL PSYCHIATRY,2017.
APA	Liu, C..,Bousman, C. A..,Pantelis, C..,Skafidas, E..,Zhang, D..,...&Everall, I. P..(2017).Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations.TRANSLATIONAL PSYCHIATRY.
MLA	Liu, C.,et al."Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations".TRANSLATIONAL PSYCHIATRY (2017).