Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia

被引：31

作者：

Wang, S. -H. ^{[1
]}

Hsiao, P. -C. ^{[2
]}

Yeh, L. -L. ^{[3
]}

Liu, C. -M. ^{[4
,5
]}

Liu, C. -C. ^{[4
,5
]}

Hwang, T. -J. ^{[4
,5
]}

Hsieh, M. H. ^{[4
,5
]}

Chien, Y. -L. ^{[4
,5
]}

Lin, Y. -T. ^{[4
,5
]}

Chandler, S. D. ^{[6
,7
]}

Faraone, S. V. ^{[8
,9
,10
,11
]}

Laird, N.

Neale, B. ^{[12
]}

McCarroll, S. A. ^{[12
]}

Glatt, S. J. ^{[8
,9
,10
,11
]}

Tsuang, M. T. ^{[6
,7
]}

Hwu, H. -G. ^{[2
,4
,5
,13
]}

Chen, W. J. ^{[2
,13
,14
,15
]}

机构：

[1] China Med Univ, Grad Inst Biostat, Taichung, Taiwan

[2] Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, 17 Xu Zhou Rd, Taipei 100, Taiwan

[3] Asia Univ, Coll Med & Hlth Sci, Dept Healthcare Adm, Taichung, Taiwan

[4] Natl Taiwan Univ, Coll Med, Dept Psychiat, Taipei, Taiwan

[5] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Taipei, Taiwan

[6] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA

[7] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[8] SUNY Upstate Med Univ, Med Genet Res Ctr, Dept Psychiat, Syracuse, NY USA

[9] SUNY Upstate Med Univ, Med Genet Res Ctr, Dept Behav Sci, Syracuse, NY USA

[10] SUNY Upstate Med Univ, Med Genet Res Ctr, Dept Neurosci & Physiol, Syracuse, NY USA

[11] Harvard Univ, Dept Biostat, Boston, MA 02115 USA

[12] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA

[13] Natl Taiwan Univ, Coll Med, Inst Brain & Mind Sci, Taipei, Taiwan

[14] Natl Taiwan Univ, Coll Publ Hlth, Dept Publ Hlth, Taipei, Taiwan

[15] Natl Taiwan Univ, Res Ctr Med Excellence, Div Genom Med, Genet Epidemiol Core Lab, Taipei, Taiwan

来源：

GENES BRAIN AND BEHAVIOR | 2018年 / 17卷 / 01期

关键词：

Polygenic risk score; schizophrenia; neurocognitive performance; GWAS; Continuous Performance Test; Wisconsin Card Sorting Test; Psychiatric Genomics Consortium; trios; PLINK; factor analyses; CARD SORTING TEST; GENOME-WIDE ASSOCIATION; WHITE-MATTER VOLUME; GENETIC OVERLAP; INTELLIGENCE; LINKAGE; METAANALYSIS; POPULATION; VARIANTS; ABILITY;

D O I：

10.1111/gbb.12401

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC-derived susceptibility variants. Schizophrenia PRS at the P-value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han-Taiwanese samples, and the score itself had a P-value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.

引用

页码：49 / 55

页数：7

共 39 条

[1]

[Anonymous], 2016, SCHIZOPHR B

[2] Genetic Overlap Among Intelligence and Other Candidate Endophenotypes for Schizophrenia [J].