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

Abstract 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 earlies...

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Autores principales:	Annemarie L. Woolston, Po-Chang Hsiao, Po-Hsiu Kuo, Shi-Heng Wang, Yin-Ju Lien, Chih-Min Liu, Hai-Gwo Hwu, Tzu-Pin Lu, Eric Y. Chuang, Li-Ching Chang, Chien-Hsiun Chen, Jer-Yuarn Wu, Ming T. Tsuang, Wei J. Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fa838836aca4b5c801de5708e982478
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spelling	oai:doaj.org-article:2fa838836aca4b5c801de5708e9824782021-12-02T11:52:39ZGenetic loci associated with an earlier age at onset in multiplex schizophrenia10.1038/s41598-017-06795-82045-2322https://doaj.org/article/2fa838836aca4b5c801de5708e9824782017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06795-8https://doaj.org/toc/2045-2322Abstract 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.Annemarie L. WoolstonPo-Chang HsiaoPo-Hsiu KuoShi-Heng WangYin-Ju LienChih-Min LiuHai-Gwo HwuTzu-Pin LuEric Y. ChuangLi-Ching ChangChien-Hsiun ChenJer-Yuarn WuMing T. TsuangWei J. ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Annemarie L. Woolston Po-Chang Hsiao Po-Hsiu Kuo Shi-Heng Wang Yin-Ju Lien Chih-Min Liu Hai-Gwo Hwu Tzu-Pin Lu Eric Y. Chuang Li-Ching Chang Chien-Hsiun Chen Jer-Yuarn Wu Ming T. Tsuang Wei J. Chen Genetic loci associated with an earlier age at onset in multiplex schizophrenia
description	Abstract 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.
format	article
author	Annemarie L. Woolston Po-Chang Hsiao Po-Hsiu Kuo Shi-Heng Wang Yin-Ju Lien Chih-Min Liu Hai-Gwo Hwu Tzu-Pin Lu Eric Y. Chuang Li-Ching Chang Chien-Hsiun Chen Jer-Yuarn Wu Ming T. Tsuang Wei J. Chen
author_facet	Annemarie L. Woolston Po-Chang Hsiao Po-Hsiu Kuo Shi-Heng Wang Yin-Ju Lien Chih-Min Liu Hai-Gwo Hwu Tzu-Pin Lu Eric Y. Chuang Li-Ching Chang Chien-Hsiun Chen Jer-Yuarn Wu Ming T. Tsuang Wei J. Chen
author_sort	Annemarie L. Woolston
title	Genetic loci associated with an earlier age at onset in multiplex schizophrenia
title_short	Genetic loci associated with an earlier age at onset in multiplex schizophrenia
title_full	Genetic loci associated with an earlier age at onset in multiplex schizophrenia
title_fullStr	Genetic loci associated with an earlier age at onset in multiplex schizophrenia
title_full_unstemmed	Genetic loci associated with an earlier age at onset in multiplex schizophrenia
title_sort	genetic loci associated with an earlier age at onset in multiplex schizophrenia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2fa838836aca4b5c801de5708e982478
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Genetic loci associated with an earlier age at onset in multiplex schizophrenia

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