Pub Date : 2025-12-02DOI: 10.1016/j.ajhg.2025.11.009
Abdalla A. Alkhawaja, Kevin W. Currin, Hannah J. Perrin, Swarooparani Vadlamudi, Amy S. Etheridge, K. Alaine Broadaway, Gabrielle H. Cannon, Carlton W. Anderson, Anne H. Moxley, Alina C. Iuga, Erin G. Schuetz, Federico Innocenti, Terrence S. Furey, Karen L. Mohlke
{"title":"Liver single-nucleus multiome profiling reveals cell-type mechanisms for cardiometabolic traits","authors":"Abdalla A. Alkhawaja, Kevin W. Currin, Hannah J. Perrin, Swarooparani Vadlamudi, Amy S. Etheridge, K. Alaine Broadaway, Gabrielle H. Cannon, Carlton W. Anderson, Anne H. Moxley, Alina C. Iuga, Erin G. Schuetz, Federico Innocenti, Terrence S. Furey, Karen L. Mohlke","doi":"10.1016/j.ajhg.2025.11.009","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.11.009","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"13 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145657121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1016/j.ajhg.2025.11.008
Qing Li, Qingyuan Song, Zhishan Chen, Jungyoon Choi, Victor Moreno, Jie Ping, Wanqing Wen, Chao Li, Xiang Shu, Jun Yan, Xiao-ou Shu, Qiuyin Cai, Jirong Long, Jeroen R. Huyghe, Rish Pai, Stephen B. Gruber, Yaohua Yang, Graham Casey, Xusheng Wang, Adetunji T. Toriola, Li Li, Bhuminder Singh, Ken S. Lau, Li Zhou, Zichen Zhang, Chong Wu, Ulrike Peters, Wei Zheng, Quan Long, Zhijun Yin, Xingyi Guo
{"title":"Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention","authors":"Qing Li, Qingyuan Song, Zhishan Chen, Jungyoon Choi, Victor Moreno, Jie Ping, Wanqing Wen, Chao Li, Xiang Shu, Jun Yan, Xiao-ou Shu, Qiuyin Cai, Jirong Long, Jeroen R. Huyghe, Rish Pai, Stephen B. Gruber, Yaohua Yang, Graham Casey, Xusheng Wang, Adetunji T. Toriola, Li Li, Bhuminder Singh, Ken S. Lau, Li Zhou, Zichen Zhang, Chong Wu, Ulrike Peters, Wei Zheng, Quan Long, Zhijun Yin, Xingyi Guo","doi":"10.1016/j.ajhg.2025.11.008","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.11.008","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"25 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145657145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.ajhg.2025.11.007
Simone Martinelli,Hélène Cavé,Alessandro De Luca,Marina DiStefano,Rachel Karchin,Ana Clara Lugones,Anne O'Donnell-Luria,Deborah I Ritter,David Tamborero,Michael Y Tolstorukov,Paulo Vidal Campregher,Marco Tartaglia,Dmitriy Sonkin
Genetic alterations influence biological function through a variety of molecular mechanisms. While common functional descriptions (such as loss of function and gain of function) are useful, they may fail to capture mechanistic complexity, particularly in cases of pleiotropy and context-dependent variant effects. To improve variant interpretation and classification, we propose a framework incorporating "context qualifiers" to address mechanistic specificity. This perspective explores the limitations of common functional descriptors and discusses the criteria needed to implement context qualifiers in variant interpretation frameworks to enhance precision medicine applications.
{"title":"Interpreting the functional impact of genetic variants: The need for context qualifiers.","authors":"Simone Martinelli,Hélène Cavé,Alessandro De Luca,Marina DiStefano,Rachel Karchin,Ana Clara Lugones,Anne O'Donnell-Luria,Deborah I Ritter,David Tamborero,Michael Y Tolstorukov,Paulo Vidal Campregher,Marco Tartaglia,Dmitriy Sonkin","doi":"10.1016/j.ajhg.2025.11.007","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.11.007","url":null,"abstract":"Genetic alterations influence biological function through a variety of molecular mechanisms. While common functional descriptions (such as loss of function and gain of function) are useful, they may fail to capture mechanistic complexity, particularly in cases of pleiotropy and context-dependent variant effects. To improve variant interpretation and classification, we propose a framework incorporating \"context qualifiers\" to address mechanistic specificity. This perspective explores the limitations of common functional descriptors and discusses the criteria needed to implement context qualifiers in variant interpretation frameworks to enhance precision medicine applications.","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"359 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.ajhg.2025.11.002
David R. Blair, Neil Risch
{"title":"Residual allelic activity likely underlies the low rates of disease expression for predicted loss-of-function variants in population-scale biobanks","authors":"David R. Blair, Neil Risch","doi":"10.1016/j.ajhg.2025.11.002","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.11.002","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"16 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1016/j.ajhg.2025.11.003
{"title":"Collaborative science in genomics: The value of data sharing and thoughtful stewardship","authors":"","doi":"10.1016/j.ajhg.2025.11.003","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.11.003","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"18 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.ajhg.2025.10.016
Diane Xue, Elizabeth E. Blue, Stephanie M. Fullerton, Nora B. Henrikson, Sarah Knerr, Anne-Marie Laberge, Lisa S. Parker, Maya Sabatello, Nirupama Nini Shridhar, Jennifer A. Smith, Benjamin S. Wilfond, Genevieve L. Wojcik, Joon-Ho Yu, Alison E. Fohner
{"title":"Training competencies and recommendations for the next generation of public health genetics: Reflections from current leaders in the field","authors":"Diane Xue, Elizabeth E. Blue, Stephanie M. Fullerton, Nora B. Henrikson, Sarah Knerr, Anne-Marie Laberge, Lisa S. Parker, Maya Sabatello, Nirupama Nini Shridhar, Jennifer A. Smith, Benjamin S. Wilfond, Genevieve L. Wojcik, Joon-Ho Yu, Alison E. Fohner","doi":"10.1016/j.ajhg.2025.10.016","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.10.016","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"5 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.ajhg.2025.10.015
Brandon Bresack, Laura Renée Kohl, Alexandra Afenjar, Frédérique Audic, Lydie Burglen, Perrine Charles, Nihal Olgac Dundar, Jiddeke van de Kamp, Keren Machol, Pilar Magoulas, Odile Goze-Martineau, Mahdi Motazacker, Heike Philippi, Alejandra Reyes, Omar A.Z. Tutakhel, Aida Bertoli-Avella, Heinrich Sticht, Rami Abou Jamra, Henry Oppermann
{"title":"Genetic variants in ESRRG are associated with a dominant non-progressive congenital movement disorder with ataxia","authors":"Brandon Bresack, Laura Renée Kohl, Alexandra Afenjar, Frédérique Audic, Lydie Burglen, Perrine Charles, Nihal Olgac Dundar, Jiddeke van de Kamp, Keren Machol, Pilar Magoulas, Odile Goze-Martineau, Mahdi Motazacker, Heike Philippi, Alejandra Reyes, Omar A.Z. Tutakhel, Aida Bertoli-Avella, Heinrich Sticht, Rami Abou Jamra, Henry Oppermann","doi":"10.1016/j.ajhg.2025.10.015","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.10.015","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"172 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1016/j.ajhg.2025.10.014
Ariane Kröll-Hermi, Corinne Stoetzel, Christelle Etard, Levon Halabelian, Elise Schaefer, Sophie Scheidecker, Kimia Kahrizi, Jamali Payman, Véronique Geoffroy, Megana Prasad, Cathy Obringer, Laurie Ruch, Amandine Girard, Hong Zeng, Fengling Li, Damien Plassard, Céline Keime, Francesca Mattioli, Claire Feger, Amélie Piton, Atsushi Fujita, Naomichi Matsumoto, Matheus Augusto Araujo Castro, Kim Chong Ae, Lyse Ruaud, Jonathan Levy, Blandine Dozières, Anne-Claude Tabet, Ingrid M. Wentzensen, Teresa Santiago-Sim, Roman Yusupov, Kristian Tveten, Marie Falkenberg Smeland, Ebba Alkhunaizi, Gina Cowing, Chumei Li, Saskia B. Wortmann, René G. Feichtinger, Johannes A. Mayr, Herman Gonorazky, Gan Jing, Xiaodong Wang, Jia Wang, Tatjana Bierhals, Lev Grinstein, Theresia Herget, Anna Ruiz, Elisabeth Gabau, Antje Kampmeier, Olivier Kassel, Alma Kuechler, Konrad Platzer, Rami Abou Jamra, Audrey Woerner, Michaela Idleburg, Susanne Gerit Kircher, Franco Laccone, Barbara Golob, Borut Peterlin, Goran Čuturilo, Velibor Tasic, Caroline M. Kolvenbach, Friedhelm Hildebrandt, Luiza L.P. Ramos, Fernando Kok, Cecilia Barbosa Buck, Ingrid M.B.H. van de Laar, Stella A. de Man, Elifcan Taşdelen, Abdullah Sezer, Afife Büke, Zehra Yavuz, Selim Selçuk Çomoğlu, Carrie Costin, Frédéric Tran Mau Them, Elodie Lacaze, Thomas Courtin, Delphine Héron, Boris Keren, Sandra Whalen, Joelle Roume, Yanzhong Yang, Mariëtte J.V. Hoffer, Arie van Haeringen, Hossein Najmabadi, Cheryl H. Arrowsmith, Uwe Strähle, Hélène Dollfus, Jean Muller
{"title":"Bi-allelic PRMT9 loss-of-function variants cause a syndromic form of intellectual disability","authors":"Ariane Kröll-Hermi, Corinne Stoetzel, Christelle Etard, Levon Halabelian, Elise Schaefer, Sophie Scheidecker, Kimia Kahrizi, Jamali Payman, Véronique Geoffroy, Megana Prasad, Cathy Obringer, Laurie Ruch, Amandine Girard, Hong Zeng, Fengling Li, Damien Plassard, Céline Keime, Francesca Mattioli, Claire Feger, Amélie Piton, Atsushi Fujita, Naomichi Matsumoto, Matheus Augusto Araujo Castro, Kim Chong Ae, Lyse Ruaud, Jonathan Levy, Blandine Dozières, Anne-Claude Tabet, Ingrid M. Wentzensen, Teresa Santiago-Sim, Roman Yusupov, Kristian Tveten, Marie Falkenberg Smeland, Ebba Alkhunaizi, Gina Cowing, Chumei Li, Saskia B. Wortmann, René G. Feichtinger, Johannes A. Mayr, Herman Gonorazky, Gan Jing, Xiaodong Wang, Jia Wang, Tatjana Bierhals, Lev Grinstein, Theresia Herget, Anna Ruiz, Elisabeth Gabau, Antje Kampmeier, Olivier Kassel, Alma Kuechler, Konrad Platzer, Rami Abou Jamra, Audrey Woerner, Michaela Idleburg, Susanne Gerit Kircher, Franco Laccone, Barbara Golob, Borut Peterlin, Goran Čuturilo, Velibor Tasic, Caroline M. Kolvenbach, Friedhelm Hildebrandt, Luiza L.P. Ramos, Fernando Kok, Cecilia Barbosa Buck, Ingrid M.B.H. van de Laar, Stella A. de Man, Elifcan Taşdelen, Abdullah Sezer, Afife Büke, Zehra Yavuz, Selim Selçuk Çomoğlu, Carrie Costin, Frédéric Tran Mau Them, Elodie Lacaze, Thomas Courtin, Delphine Héron, Boris Keren, Sandra Whalen, Joelle Roume, Yanzhong Yang, Mariëtte J.V. Hoffer, Arie van Haeringen, Hossein Najmabadi, Cheryl H. Arrowsmith, Uwe Strähle, Hélène Dollfus, Jean Muller","doi":"10.1016/j.ajhg.2025.10.014","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.10.014","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"8 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.ajhg.2025.10.017
Meer Jacob Rahimi, Nicole Urban, Meret Wegler, Heinrich Sticht, Michael Schaefer, Bernt Popp, Frank Gaunitz, Manuela Morleo, Vincenzo Nigro, Silvia Maitz, Grazia M.S. Mancini, Claudia Ruivenkamp, Eun-Kyung Suk, Tobias Bartolomaeus, Andreas Merkenschlager, Daniel Koboldt, Dennis Bartholomew, Alexander P.A. Stegmann, Margje Sinnema, Irma Duynisveld, Ramona Salvarinova, Simone Race, Bert B.A. de Vries, Aurélien Trimouille, Sophie Naudion, Daphna Marom, Uri Hamiel, Noa Henig, Florence Demurger, Nils Rahner, Enrika Bartels, J. Austin Hamm, Abbey M. Putnam, Richard Person, Rami Abou Jamra, Henry Oppermann
{"title":"De novo variants in ATP2B1 lead to neurodevelopmental delay","authors":"Meer Jacob Rahimi, Nicole Urban, Meret Wegler, Heinrich Sticht, Michael Schaefer, Bernt Popp, Frank Gaunitz, Manuela Morleo, Vincenzo Nigro, Silvia Maitz, Grazia M.S. Mancini, Claudia Ruivenkamp, Eun-Kyung Suk, Tobias Bartolomaeus, Andreas Merkenschlager, Daniel Koboldt, Dennis Bartholomew, Alexander P.A. Stegmann, Margje Sinnema, Irma Duynisveld, Ramona Salvarinova, Simone Race, Bert B.A. de Vries, Aurélien Trimouille, Sophie Naudion, Daphna Marom, Uri Hamiel, Noa Henig, Florence Demurger, Nils Rahner, Enrika Bartels, J. Austin Hamm, Abbey M. Putnam, Richard Person, Rami Abou Jamra, Henry Oppermann","doi":"10.1016/j.ajhg.2025.10.017","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.10.017","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"85 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.ajhg.2025.10.012
David Wang, Matthew R. Gazzara, San Jewell, Benjamin D. Wales-McGrath, Kevin Yang, Christopher D. Brown, Peter S. Choi, Yoseph Barash
{"title":"A deep dive into statistical modeling of RNA splicing QTLs reveals variants that explain neurodegenerative disease","authors":"David Wang, Matthew R. Gazzara, San Jewell, Benjamin D. Wales-McGrath, Kevin Yang, Christopher D. Brown, Peter S. Choi, Yoseph Barash","doi":"10.1016/j.ajhg.2025.10.012","DOIUrl":"https://doi.org/10.1016/j.ajhg.2025.10.012","url":null,"abstract":"","PeriodicalId":7659,"journal":{"name":"American journal of human genetics","volume":"51 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：