Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer’s disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.
{"title":"Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer’s disease","authors":"Yu Guo, Shi-Dong Chen, Jia You, Shu-Yi Huang, Yi-Lin Chen, Yi Zhang, Lin-Bo Wang, Xiao-Yu He, Yue-Ting Deng, Ya-Ru Zhang, Yu-Yuan Huang, Qiang Dong, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu","doi":"10.1038/s41562-024-01924-6","DOIUrl":"https://doi.org/10.1038/s41562-024-01924-6","url":null,"abstract":"<p>Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer’s disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.</p>","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":29.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141566301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.1038/s41562-024-01947-z
Alessandro Sparacio, Hans IJzerman, Ivan Ropovik, Filippo Giorgini, Christoph Spiessens, Bert N Uchino, Joshua Landvatter, Tracey Tacana, Sandra J Diller, Jaye L Derrick, Joahana Segundo, Jace D Pierce, Robert M Ross, Zoë Francis, Amanda LaBoucane, Christine Ma-Kellams, Maire B Ford, Kathleen Schmidt, Celia C Wong, Wendy C Higgins, Bryant M Stone, Samantha K Stanley, Gianni Ribeiro, Paul T Fuglestad, Valerie Jaklin, Andrea Kübler, Philipp Ziebell, Crystal L Jewell, Yulia Kovas, Mahnoosh Allahghadri, Charlotte Fransham, Michael F Baranski, Hannah Burgess, Annika B E Benz, Maysa DeSousa, Catherine E Nylin, Janae C Brooks, Caitlyn M Goldsmith, Jessica M Benson, Siobhán M Griffin, Stephen Dunne, William E Davis, Tam J Watermeyer, William B Meese, Jennifer L Howell, Laurel Standiford Reyes, Megan G Strickland, Sally S Dickerson, Samantha Pescatore, Shayna Skakoon-Sparling, Zachary I Wunder, Martin V Day, Shawna Brenton, Audrey H Linden, Christopher E Hawk, Léan V O'Brien, Tenzin Urgyen, Jennifer S McDonald, Kim Lien van der Schans, Heidi Blocker, Caroline Ng Tseung-Wong, Gabriela M Jiga-Boy
{"title":"Author Correction: Self-administered mindfulness interventions reduce stress in a large, randomized controlled multi-site study.","authors":"Alessandro Sparacio, Hans IJzerman, Ivan Ropovik, Filippo Giorgini, Christoph Spiessens, Bert N Uchino, Joshua Landvatter, Tracey Tacana, Sandra J Diller, Jaye L Derrick, Joahana Segundo, Jace D Pierce, Robert M Ross, Zoë Francis, Amanda LaBoucane, Christine Ma-Kellams, Maire B Ford, Kathleen Schmidt, Celia C Wong, Wendy C Higgins, Bryant M Stone, Samantha K Stanley, Gianni Ribeiro, Paul T Fuglestad, Valerie Jaklin, Andrea Kübler, Philipp Ziebell, Crystal L Jewell, Yulia Kovas, Mahnoosh Allahghadri, Charlotte Fransham, Michael F Baranski, Hannah Burgess, Annika B E Benz, Maysa DeSousa, Catherine E Nylin, Janae C Brooks, Caitlyn M Goldsmith, Jessica M Benson, Siobhán M Griffin, Stephen Dunne, William E Davis, Tam J Watermeyer, William B Meese, Jennifer L Howell, Laurel Standiford Reyes, Megan G Strickland, Sally S Dickerson, Samantha Pescatore, Shayna Skakoon-Sparling, Zachary I Wunder, Martin V Day, Shawna Brenton, Audrey H Linden, Christopher E Hawk, Léan V O'Brien, Tenzin Urgyen, Jennifer S McDonald, Kim Lien van der Schans, Heidi Blocker, Caroline Ng Tseung-Wong, Gabriela M Jiga-Boy","doi":"10.1038/s41562-024-01947-z","DOIUrl":"10.1038/s41562-024-01947-z","url":null,"abstract":"","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":21.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1038/s41562-024-01925-5
Ernestine Gheyoh Ndzi
Unsupportive university policies force parents to make choices about how to feed their baby. Ernestine Gheyoh Ndzi, an expert in employment law and advocate for parental rights in the UK, tells us why this needs to change.
{"title":"I want universities to put breastfeeding on their gender pay gap agenda","authors":"Ernestine Gheyoh Ndzi","doi":"10.1038/s41562-024-01925-5","DOIUrl":"10.1038/s41562-024-01925-5","url":null,"abstract":"Unsupportive university policies force parents to make choices about how to feed their baby. Ernestine Gheyoh Ndzi, an expert in employment law and advocate for parental rights in the UK, tells us why this needs to change.","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":21.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1038/s41562-024-01909-5
Caitlin E. Carey, Rebecca Shafee, Robbee Wedow, Amanda Elliott, Duncan S. Palmer, John Compitello, Masahiro Kanai, Liam Abbott, Patrick Schultz, Konrad J. Karczewski, Samuel C. Bryant, Caroline M. Cusick, Claire Churchhouse, Daniel P. Howrigan, Daniel King, George Davey Smith, Benjamin M. Neale, Raymond K. Walters, Elise B. Robinson
Data within biobanks capture broad yet detailed indices of human variation, but biobank-wide insights can be difficult to extract due to complexity and scale. Here, using large-scale factor analysis, we distill hundreds of variables (diagnoses, assessments and survey items) into 35 latent constructs, using data from unrelated individuals with predominantly estimated European genetic ancestry in UK Biobank. These factors recapitulate known disease classifications, disentangle elements of socioeconomic status, highlight the relevance of psychiatric constructs to health and improve measurement of pro-health behaviours. We go on to demonstrate the power of this approach to clarify genetic signal, enhance discovery and identify associations between underlying phenotypic structure and health outcomes. In building a deeper understanding of ways in which constructs such as socioeconomic status, trauma, or physical activity are structured in the dataset, we emphasize the importance of considering the interwoven nature of the human phenome when evaluating public health patterns. Carey and colleagues reveal 35 major latent constructs (factors) in the phenotype data of unrelated individuals with predominantly estimated European genetic ancestry from UK Biobank.
{"title":"Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation","authors":"Caitlin E. Carey, Rebecca Shafee, Robbee Wedow, Amanda Elliott, Duncan S. Palmer, John Compitello, Masahiro Kanai, Liam Abbott, Patrick Schultz, Konrad J. Karczewski, Samuel C. Bryant, Caroline M. Cusick, Claire Churchhouse, Daniel P. Howrigan, Daniel King, George Davey Smith, Benjamin M. Neale, Raymond K. Walters, Elise B. Robinson","doi":"10.1038/s41562-024-01909-5","DOIUrl":"10.1038/s41562-024-01909-5","url":null,"abstract":"Data within biobanks capture broad yet detailed indices of human variation, but biobank-wide insights can be difficult to extract due to complexity and scale. Here, using large-scale factor analysis, we distill hundreds of variables (diagnoses, assessments and survey items) into 35 latent constructs, using data from unrelated individuals with predominantly estimated European genetic ancestry in UK Biobank. These factors recapitulate known disease classifications, disentangle elements of socioeconomic status, highlight the relevance of psychiatric constructs to health and improve measurement of pro-health behaviours. We go on to demonstrate the power of this approach to clarify genetic signal, enhance discovery and identify associations between underlying phenotypic structure and health outcomes. In building a deeper understanding of ways in which constructs such as socioeconomic status, trauma, or physical activity are structured in the dataset, we emphasize the importance of considering the interwoven nature of the human phenome when evaluating public health patterns. Carey and colleagues reveal 35 major latent constructs (factors) in the phenotype data of unrelated individuals with predominantly estimated European genetic ancestry from UK Biobank.","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":21.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41562-024-01909-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1038/s41562-024-01913-9
Maria A. Caffrey
This year, 49% of the world will go to the polls. Political support for science-informed policy is not a given. Maria Caffrey, a whistleblower who defended scientific integrity under the Trump administration, offers advice on media engagement during this time.
{"title":"Why scientific integrity matters now more than ever","authors":"Maria A. Caffrey","doi":"10.1038/s41562-024-01913-9","DOIUrl":"10.1038/s41562-024-01913-9","url":null,"abstract":"This year, 49% of the world will go to the polls. Political support for science-informed policy is not a given. Maria Caffrey, a whistleblower who defended scientific integrity under the Trump administration, offers advice on media engagement during this time.","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":21.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141495891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1038/s41562-024-01937-1
Biray Kolluoglu, Lale Akarun
{"title":"Author Correction: Standing up for the university","authors":"Biray Kolluoglu, Lale Akarun","doi":"10.1038/s41562-024-01937-1","DOIUrl":"10.1038/s41562-024-01937-1","url":null,"abstract":"","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":21.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41562-024-01937-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1038/s41562-024-01918-4
Nicole C. Kelp, Ashley A. Anderson, Joy C. Enyinnaya
Science communication often assumes a ‘deficit’ in knowledge on behalf of the recipient, but this deficit-based approach is inequitable and ineffective. We must train all STEM (science, technology, engineering and mathematics) students in inclusive science communication, which uses collaboration with diverse people to address misinformation and solve socioscientific issues.
{"title":"All STEM students should learn inclusive science communication","authors":"Nicole C. Kelp, Ashley A. Anderson, Joy C. Enyinnaya","doi":"10.1038/s41562-024-01918-4","DOIUrl":"10.1038/s41562-024-01918-4","url":null,"abstract":"Science communication often assumes a ‘deficit’ in knowledge on behalf of the recipient, but this deficit-based approach is inequitable and ineffective. We must train all STEM (science, technology, engineering and mathematics) students in inclusive science communication, which uses collaboration with diverse people to address misinformation and solve socioscientific issues.","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":21.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141495865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41562-024-01903-x
Bei Zhang, Jia You, Edmund T. Rolls, Xiang Wang, Jujiao Kang, Yuzhu Li, Ruohan Zhang, Wei Zhang, Huifu Wang, Shitong Xiang, Chun Shen, Yuchao Jiang, Chao Xie, Jintai Yu, Wei Cheng, Jianfeng Feng
Suicide is a global public health challenge, yet considerable uncertainty remains regarding the associations of both behaviour-related and physiological factors with suicide attempts (SA). Here we first estimated polygenic risk scores (PRS) for SA in 334,706 UK Biobank participants and conducted phenome-wide association analyses considering 2,291 factors. We identified 246 (63.07%) behaviour-related and 200 (10.41%, encompassing neuroimaging, blood and metabolic biomarkers, and proteins) physiological factors significantly associated with SA-PRS, with robust associations observed in lifestyle factors and mental health. Further case–control analyses involving 3,558 SA cases and 149,976 controls mirrored behaviour-related associations observed with SA-PRS. Moreover, Mendelian randomization analyses supported a potential causal effect of liability to 58 factors on SA, such as age at first intercourse, neuroticism, smoking, overall health rating and depression. Notably, machine-learning classification models based on behaviour-related factors exhibited high discriminative accuracy in distinguishing those with and without SA (area under the receiver operating characteristic curve 0.909 ± 0.006). This study provides comprehensive insights into diverse risk factors for SA, shedding light on potential avenues for targeted prevention and intervention strategies.
自杀是一项全球性的公共卫生挑战，但行为相关因素和生理因素与自杀未遂（SA）之间的关联仍存在很大的不确定性。在此，我们首先估算了 334 706 名英国生物库参与者的自杀未遂多基因风险评分（PRS），并对 2291 个因素进行了全表型关联分析。我们确定了 246 个（占 63.07%）行为相关因素和 200 个（占 10.41%，包括神经影像学、血液和代谢生物标志物以及蛋白质）生理因素与 SA-PRS 显著相关，并观察到生活方式因素和心理健康因素之间的密切关联。涉及 3,558 例 SA 病例和 149,976 例对照的进一步病例对照分析也反映了与 SA-PRS 有关的行为相关性。此外，孟德尔随机分析支持了 58 个因素对 SA 的潜在因果效应，如初次性交年龄、神经质、吸烟、总体健康评分和抑郁。值得注意的是，基于行为相关因素的机器学习分类模型在区分有SA和无SA的人群方面表现出很高的鉴别准确性（接收者操作特征曲线下面积为0.909 ± 0.006）。这项研究全面揭示了导致 SA 的各种风险因素，为制定有针对性的预防和干预策略提供了潜在途径。
{"title":"Identifying behaviour-related and physiological risk factors for suicide attempts in the UK Biobank","authors":"Bei Zhang, Jia You, Edmund T. Rolls, Xiang Wang, Jujiao Kang, Yuzhu Li, Ruohan Zhang, Wei Zhang, Huifu Wang, Shitong Xiang, Chun Shen, Yuchao Jiang, Chao Xie, Jintai Yu, Wei Cheng, Jianfeng Feng","doi":"10.1038/s41562-024-01903-x","DOIUrl":"https://doi.org/10.1038/s41562-024-01903-x","url":null,"abstract":"<p>Suicide is a global public health challenge, yet considerable uncertainty remains regarding the associations of both behaviour-related and physiological factors with suicide attempts (SA). Here we first estimated polygenic risk scores (PRS) for SA in 334,706 UK Biobank participants and conducted phenome-wide association analyses considering 2,291 factors. We identified 246 (63.07%) behaviour-related and 200 (10.41%, encompassing neuroimaging, blood and metabolic biomarkers, and proteins) physiological factors significantly associated with SA-PRS, with robust associations observed in lifestyle factors and mental health. Further case–control analyses involving 3,558 SA cases and 149,976 controls mirrored behaviour-related associations observed with SA-PRS. Moreover, Mendelian randomization analyses supported a potential causal effect of liability to 58 factors on SA, such as age at first intercourse, neuroticism, smoking, overall health rating and depression. Notably, machine-learning classification models based on behaviour-related factors exhibited high discriminative accuracy in distinguishing those with and without SA (area under the receiver operating characteristic curve 0.909 ± 0.006). This study provides comprehensive insights into diverse risk factors for SA, shedding light on potential avenues for targeted prevention and intervention strategies.</p>","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":29.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1038/s41562-024-01917-5
Guoyu Wang
Guoyu Wang leads and serves on Chinese ethics committees. She explains how research ethics have developed in China, and why ethics review promotes responsible innovation.
{"title":"Ethics committees promote responsible research in China","authors":"Guoyu Wang","doi":"10.1038/s41562-024-01917-5","DOIUrl":"10.1038/s41562-024-01917-5","url":null,"abstract":"Guoyu Wang leads and serves on Chinese ethics committees. She explains how research ethics have developed in China, and why ethics review promotes responsible innovation.","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":21.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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