Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia

Abstract Patients with schizophrenia display characteristic smoking-related behaviors and genetic correlations between smoking behaviors and schizophrenia have been identified in European individuals. However, the genetic etiology of the association remains to be clarified. The present study investi...

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Autores principales:	Kazutaka Ohi, Daisuke Nishizawa, Yukimasa Muto, Shunsuke Sugiyama, Junko Hasegawa, Midori Soda, Kiyoyuki Kitaichi, Ryota Hashimoto, Toshiki Shioiri, Kazutaka Ikeda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/05b31cf2659b456d925069409e0c92a9
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spelling	oai:doaj.org-article:05b31cf2659b456d925069409e0c92a92021-12-02T16:19:50ZPolygenic risk scores for late smoking initiation associated with the risk of schizophrenia10.1038/s41537-020-00126-z2334-265Xhttps://doaj.org/article/05b31cf2659b456d925069409e0c92a92020-11-01T00:00:00Zhttps://doi.org/10.1038/s41537-020-00126-zhttps://doaj.org/toc/2334-265XAbstract Patients with schizophrenia display characteristic smoking-related behaviors and genetic correlations between smoking behaviors and schizophrenia have been identified in European individuals. However, the genetic etiology of the association remains to be clarified. The present study investigated transethnic genetic overlaps between European-based smoking behaviors and the risk of Japanese schizophrenia by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 24,114–74,035) related to four smoking-related intermediate phenotypes [(i) smoking initiation, (ii) age at smoking initiation, (iii) smoking quantity, and (iv) smoking cessation] were utilized as discovery samples. PRSs derived from these discovery GWASs were calculated for 332 Japanese subjects [schizophrenia patients, their unaffected first-degree relatives (FRs), and healthy controls (HCs)] as a target sample. Based on GWASs of European smoking phenotypes, we investigated the effects of PRSs on smoking phenotypes and the risk of schizophrenia in the Japanese population. Of the four smoking-related behaviors, the PRSs for age at smoking initiation in Europeans significantly predicted the age at smoking initiation (R 2 = 0.049, p = 0.026) and the PRSs for smoking cessation significantly predicted the smoking cessation (R 2 = 0.092, p = 0.027) in Japanese ever-smokers. Furthermore, the PRSs related to age at smoking initiation in Europeans were higher in Japanese schizophrenia patients than in the HCs and those of the FRs were intermediate between those of patients with schizophrenia and those of the HCs (R 2 = 0.015, p = 0.015). In our target subjects, patients with schizophrenia had a higher mean age at smoking initiation (p = 0.018) and rate of daily smoking initiation after age 20 years (p = 0.023) compared with the HCs. A total of 60.6% of the patients started to smoke before the onset of schizophrenia. These findings suggest that genetic factors affecting late smoking initiation are associated with the risk of schizophrenia.Kazutaka OhiDaisuke NishizawaYukimasa MutoShunsuke SugiyamaJunko HasegawaMidori SodaKiyoyuki KitaichiRyota HashimotoToshiki ShioiriKazutaka IkedaNature PortfolioarticlePsychiatryRC435-571ENnpj Schizophrenia, Vol 6, Iss 1, Pp 1-7 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Psychiatry RC435-571
spellingShingle	Psychiatry RC435-571 Kazutaka Ohi Daisuke Nishizawa Yukimasa Muto Shunsuke Sugiyama Junko Hasegawa Midori Soda Kiyoyuki Kitaichi Ryota Hashimoto Toshiki Shioiri Kazutaka Ikeda Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia
description	Abstract Patients with schizophrenia display characteristic smoking-related behaviors and genetic correlations between smoking behaviors and schizophrenia have been identified in European individuals. However, the genetic etiology of the association remains to be clarified. The present study investigated transethnic genetic overlaps between European-based smoking behaviors and the risk of Japanese schizophrenia by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 24,114–74,035) related to four smoking-related intermediate phenotypes [(i) smoking initiation, (ii) age at smoking initiation, (iii) smoking quantity, and (iv) smoking cessation] were utilized as discovery samples. PRSs derived from these discovery GWASs were calculated for 332 Japanese subjects [schizophrenia patients, their unaffected first-degree relatives (FRs), and healthy controls (HCs)] as a target sample. Based on GWASs of European smoking phenotypes, we investigated the effects of PRSs on smoking phenotypes and the risk of schizophrenia in the Japanese population. Of the four smoking-related behaviors, the PRSs for age at smoking initiation in Europeans significantly predicted the age at smoking initiation (R 2 = 0.049, p = 0.026) and the PRSs for smoking cessation significantly predicted the smoking cessation (R 2 = 0.092, p = 0.027) in Japanese ever-smokers. Furthermore, the PRSs related to age at smoking initiation in Europeans were higher in Japanese schizophrenia patients than in the HCs and those of the FRs were intermediate between those of patients with schizophrenia and those of the HCs (R 2 = 0.015, p = 0.015). In our target subjects, patients with schizophrenia had a higher mean age at smoking initiation (p = 0.018) and rate of daily smoking initiation after age 20 years (p = 0.023) compared with the HCs. A total of 60.6% of the patients started to smoke before the onset of schizophrenia. These findings suggest that genetic factors affecting late smoking initiation are associated with the risk of schizophrenia.
format	article
author	Kazutaka Ohi Daisuke Nishizawa Yukimasa Muto Shunsuke Sugiyama Junko Hasegawa Midori Soda Kiyoyuki Kitaichi Ryota Hashimoto Toshiki Shioiri Kazutaka Ikeda
author_facet	Kazutaka Ohi Daisuke Nishizawa Yukimasa Muto Shunsuke Sugiyama Junko Hasegawa Midori Soda Kiyoyuki Kitaichi Ryota Hashimoto Toshiki Shioiri Kazutaka Ikeda
author_sort	Kazutaka Ohi
title	Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia
title_short	Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia
title_full	Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia
title_fullStr	Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia
title_full_unstemmed	Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia
title_sort	polygenic risk scores for late smoking initiation associated with the risk of schizophrenia
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/05b31cf2659b456d925069409e0c92a9
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Polygenic risk scores for late smoking initiation associated with the risk of schizophrenia

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