Genetic loci associated with an earlier age at onset in multiplex schizophrenia

被引:10
作者
Woolston, Annemarie L. [1 ]
Hsiao, Po-Chang [2 ]
Kuo, Po-Hsiu [1 ,2 ,3 ]
Wang, Shi-Heng [1 ,4 ]
Lien, Yin-Ju [5 ]
Liu, Chih-Min [6 ,7 ,8 ]
Hwu, Hai-Gwo [1 ,6 ,7 ]
Lu, Tzu-Pin [1 ,9 ]
Chuang, Eric Y. [9 ,10 ]
Chang, Li-Ching [11 ]
Chen, Chien-Hsiun [11 ]
Wu, Jer-Yuarn [11 ]
Tsuang, Ming T. [12 ,13 ,14 ,15 ]
Chen, Wei J. [1 ,2 ,6 ,7 ,8 ]
机构
[1] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Coll Publ Hlth, Taipei 100, Taiwan
[2] Natl Taiwan Univ, Ctr Genom Med, Genet Epidemiol Core, Taipei 100, Taiwan
[3] Natl Taiwan Univ, Coll Publ Hlth, Res Ctr Genes Environm & Human Hlth, Taipei 100, Taiwan
[4] China Med Univ, Grad Inst Biostat, Taichung 404, Taiwan
[5] Natl Taiwan Normal Univ, Dept Hlth Promot & Hlth Educ, Coll Educ, Taipei 106, Taiwan
[6] Natl Taiwan Univ, Dept Psychiat, Coll Med, Taipei 100, Taiwan
[7] Natl Taiwan Univ, Natl Univ Hosp, Taipei 100, Taiwan
[8] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Grad Inst Brain & Mind Sci, Coll Med, Taipei 100, Taiwan
[9] Natl Taiwan Univ, Ctr Genom Med Bioinformat & Biostat Core, Taipei 100, Taiwan
[10] Natl Taiwan Univ, Coll Elect Engn & Comp Sci, Grad Inst Biomed Elect & Bioinformat, Taipei 106, Taiwan
[11] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan
[12] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA
[13] Inst Genom Med, Dept Psychiat, La Jolla, CA 92093 USA
[14] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA
[15] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
GENOME-WIDE ASSOCIATION; PARKINSONS-DISEASE; LINKAGE; METAANALYSIS; TAIWAN; HETEROGENEITY; SYMPTOMS; DESIGN; POWER; RISK;
D O I
10.1038/s41598-017-06795-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
An earlier age at onset (AAO) has been associated with greater genetic loadings in schizophrenia. This study aimed to identify modifier loci associated with an earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was conducted in 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores (GRS) composed of the candidate loci were used to distinguish patients with an early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands. When 132 patients with an earlier AAO and 158 patients with a later AAO were included, a significant trend in the 14-SNP GRS was detected among those unrelated probands from 4 family groups with the earliest, earlier, later, and latest AAO. The overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co-affected siblings of the GWAS probands and trend effect across unrelated patients. Preliminary network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson's disease and schizophrenia research.
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页数:9
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