Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging

Abstract To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Ta...

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Main Authors: Chi-Shin Wu, Chia-Lin Hsu, Mei-Chen Lin, Mei-Hsin Su, Yen-Feng Lin, Chia-Yen Chen, Po-Chang Hsiao, Yi-Jiun Pan, Pei-Chun Chen, Yen-Tsung Huang, Shi-Heng Wang
Format: Article
Language:English
Published: Nature Publishing Group 2024-11-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-024-03182-6
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author Chi-Shin Wu
Chia-Lin Hsu
Mei-Chen Lin
Mei-Hsin Su
Yen-Feng Lin
Chia-Yen Chen
Po-Chang Hsiao
Yi-Jiun Pan
Pei-Chun Chen
Yen-Tsung Huang
Shi-Heng Wang
author_facet Chi-Shin Wu
Chia-Lin Hsu
Mei-Chen Lin
Mei-Hsin Su
Yen-Feng Lin
Chia-Yen Chen
Po-Chang Hsiao
Yi-Jiun Pan
Pei-Chun Chen
Yen-Tsung Huang
Shi-Heng Wang
author_sort Chi-Shin Wu
collection DOAJ
description Abstract To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Taiwan Biobank, we calculated the polygenic risk score (PRS) for SCZ (PRSSCZ) and BPD (PRSBPD), shared PRS between SCZ and BPD (PRSSCZ+BPD), and SCZ-specific PRS (PRSSCZvsBPD). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRSSCZ was split into PRSSCZ_concordant/PRSSCZ_discordant, and PRSBPD was split into PRSBPD_concordant/PRSBPD_discordant. Ordinal logistic regression models were used to estimate the association with educational attainment. Linear regression models were used to estimate the associations with cognitive aging (n = 27,005), measured by the Mini-Mental State Examination (MMSE), and with MMSE change (n = 6194 with mean follow-up duration of 3.9 y) in individuals aged≥ 60 years. PRSSCZ, PRSBPD, and PRSSCZ+BPD were positively associated with educational attainment, whereas PRSSCZvsBPD was negatively associated with educational attainment. PRSSCZ was negatively associated with MMSE, while PRSBPD was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRSSCZ_concordant and PRSBPD_concordant mainly determined these effects mentioned above. PRSSCZvsBPD predicted decreases in the MMSE scores. Using a large collection of community samples, this study provided evidence for the contrasting effects of polygenic architecture in SCZ and BPD on educational attainment and cognitive aging and suggested that SCZ and BPD were not genetically homogeneous.
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spelling doaj-art-f5af8cde86504d55baa4d61db59c658b2024-11-17T12:50:02ZengNature Publishing GroupTranslational Psychiatry2158-31882024-11-011411810.1038/s41398-024-03182-6Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive agingChi-Shin Wu0Chia-Lin Hsu1Mei-Chen Lin2Mei-Hsin Su3Yen-Feng Lin4Chia-Yen Chen5Po-Chang Hsiao6Yi-Jiun Pan7Pei-Chun Chen8Yen-Tsung Huang9Shi-Heng Wang10National Center for Geriatrics and Welfare Research, National Health Research InstitutesCollege of Public Health, China Medical UniversityNational Center for Geriatrics and Welfare Research, National Health Research InstitutesCollege of Public Health, China Medical UniversityCenter for Neuropsychiatric Research, National Health Research InstitutesBiogenCollege of Public Health, National Taiwan UniversitySchool of Medicine, College of Medicine, China Medical UniversityNational Center for Geriatrics and Welfare Research, National Health Research InstitutesInstitute of Statistical Science, Academia SinicaNational Center for Geriatrics and Welfare Research, National Health Research InstitutesAbstract To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Taiwan Biobank, we calculated the polygenic risk score (PRS) for SCZ (PRSSCZ) and BPD (PRSBPD), shared PRS between SCZ and BPD (PRSSCZ+BPD), and SCZ-specific PRS (PRSSCZvsBPD). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRSSCZ was split into PRSSCZ_concordant/PRSSCZ_discordant, and PRSBPD was split into PRSBPD_concordant/PRSBPD_discordant. Ordinal logistic regression models were used to estimate the association with educational attainment. Linear regression models were used to estimate the associations with cognitive aging (n = 27,005), measured by the Mini-Mental State Examination (MMSE), and with MMSE change (n = 6194 with mean follow-up duration of 3.9 y) in individuals aged≥ 60 years. PRSSCZ, PRSBPD, and PRSSCZ+BPD were positively associated with educational attainment, whereas PRSSCZvsBPD was negatively associated with educational attainment. PRSSCZ was negatively associated with MMSE, while PRSBPD was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRSSCZ_concordant and PRSBPD_concordant mainly determined these effects mentioned above. PRSSCZvsBPD predicted decreases in the MMSE scores. Using a large collection of community samples, this study provided evidence for the contrasting effects of polygenic architecture in SCZ and BPD on educational attainment and cognitive aging and suggested that SCZ and BPD were not genetically homogeneous.https://doi.org/10.1038/s41398-024-03182-6
spellingShingle Chi-Shin Wu
Chia-Lin Hsu
Mei-Chen Lin
Mei-Hsin Su
Yen-Feng Lin
Chia-Yen Chen
Po-Chang Hsiao
Yi-Jiun Pan
Pei-Chun Chen
Yen-Tsung Huang
Shi-Heng Wang
Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging
Translational Psychiatry
title Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging
title_full Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging
title_fullStr Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging
title_full_unstemmed Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging
title_short Association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging
title_sort association of polygenic liabilities for schizophrenia and bipolar disorder with educational attainment and cognitive aging
url https://doi.org/10.1038/s41398-024-03182-6
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