Nature genetics最新文献

{"title":"Publisher Correction: A genome-wide association analysis reveals new pathogenic pathways in gout","authors":"Tanya J. Major, Riku Takei, Hirotaka Matsuo, Megan P. Leask, Nicholas A. Sumpter, Ruth K. Topless, Yuya Shirai, Wei Wang, Murray J. Cadzow, Amanda J. Phipps-Green, Zhiqiang Li, Aichang Ji, Marilyn E. Merriman, Emily Morice, Eric E. Kelley, Wen-Hua Wei, Sally P. A. McCormick, Matthew J. Bixley, Richard J. Reynolds, Kenneth G. Saag, Tayaza Fadason, Evgenia Golovina, Justin M. O’Sullivan, Lisa K. Stamp, Nicola Dalbeth, Abhishek Abhishek, Michael Doherty, Edward Roddy, Lennart T. H. Jacobsson, Meliha C. Kapetanovic, Olle Melander, Mariano Andrés, Fernando Pérez-Ruiz, Rosa J. Torres, Timothy Radstake, Timothy L. Jansen, Matthijs Janssen, Leo A. B. Joosten, Ruiqi Liu, Orsolya I. Gaal, Tania O. Crişan, Simona Rednic, Fina Kurreeman, Tom W. J. Huizinga, René Toes, Frédéric Lioté, Pascal Richette, Thomas Bardin, Hang Korng Ea, Tristan Pascart, Geraldine M. McCarthy, Laura Helbert, Blanka Stibůrková, Anne-K. Tausche, Till Uhlig, Véronique Vitart, Thibaud S. Boutin, Caroline Hayward, Philip L. Riches, Stuart H. Ralston, Archie Campbell, Thomas M. MacDonald, FAST Study Group, Akiyoshi Nakayama, Tappei Takada, Masahiro Nakatochi, Seiko Shimizu, Yusuke Kawamura, Yu Toyoda, Hirofumi Nakaoka, Ken Yamamoto, Keitaro Matsuo, Nariyoshi Shinomiya, Kimiyoshi Ichida, Japan Gout Genomics Consortium, Chaeyoung Lee, Asia Pacific Gout Consortium, Linda A. Bradbury, Matthew A. Brown, Philip C. Robinson, Russell R. C. Buchanan, Catherine L. Hill, Susan Lester, Malcolm D. Smith, Maureen Rischmueller, Hyon K. Choi, Eli A. Stahl, Jeff N. Miner, Daniel H. Solomon, Jing Cui, Kathleen M. Giacomini, Deanna J. Brackman, Eric M. Jorgenson, GlobalGout Genetics Consortium, Hongbo Liu, Katalin Susztak, 23andMe Research Team, Suyash Shringarpure, Alexander So, Yukinori Okada, Changgui Li, Yongyong Shi, Tony R. Merriman","doi":"10.1038/s41588-024-02017-w","DOIUrl":"10.1038/s41588-024-02017-w","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2577-2577"},"PeriodicalIF":31.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02017-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ZmCPK39–ZmDi19–ZmPR10 immune module regulates quantitative resistance to multiple foliar diseases in maize","authors":"Mang Zhu, Tao Zhong, Ling Xu, Chenyu Guo, Xiaohui Zhang, Yulin Liu, Yan Zhang, Yancong Li, Zhijian Xie, Tingting Liu, Fuyan Jiang, Xingming Fan, Peter Balint-Kurti, Mingliang Xu","doi":"10.1038/s41588-024-01968-4","DOIUrl":"10.1038/s41588-024-01968-4","url":null,"abstract":"Gray leaf spot, northern leaf blight and southern leaf blight are three of the most destructive foliar diseases affecting maize (Zea mays L.). Here we identified a gene, ZmCPK39, that encodes a calcium-dependent protein kinase and negatively regulates quantitative resistance to these three diseases. The ZmCPK39 allele in the resistant line displayed significantly lower pathogen-induced gene expression than that in the susceptible line. A marked decrease in ZmCPK39 abundance mitigated the phosphorylation and degradation of the transcription factor ZmDi19. This led to elevated expression of ZmPR10, a gene known to encode an antimicrobial protein, thereby enhancing maize resistance to foliar diseases. Moreover, the F1 hybrid with reduced ZmCPK39 expression favored disease resistance, thereby increasing yield. Hence, the discovery of the ZmCPK39–ZmDi19–ZmPR10 immune module provides insight into the mechanisms underlying broad-spectrum quantitative disease resistance and also offers a new avenue for the genetic control of maize foliar diseases. A calcium-dependent protein kinase ZmCPK39 regulates quantitative resistance to multiple foliar diseases in maize through the ZmCPK39–ZmDi19–ZmPR10 immune module.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2815-2826"},"PeriodicalIF":31.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01968-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer’s disease","authors":"Yuchang Wu, Zhongxuan Sun, Qinwen Zheng, Jiacheng Miao, Stephen Dorn, Shubhabrata Mukherjee, Jason M. Fletcher, Qiongshi Lu","doi":"10.1038/s41588-024-01963-9","DOIUrl":"10.1038/s41588-024-01963-9","url":null,"abstract":"Almost every recent Alzheimer’s disease (AD) genome-wide association study (GWAS) has performed meta-analysis to combine studies with clinical diagnosis of AD with studies that use proxy phenotypes based on parental disease history. Here, we report major limitations in current GWAS-by-proxy (GWAX) practices due to uncorrected survival bias and nonrandom participation in parental illness surveys, which cause substantial discrepancies between AD GWAS and GWAX results. We demonstrate that the current AD GWAX provide highly misleading genetic correlations between AD risk and higher education, which subsequently affects a variety of genetic epidemiological applications involving AD and cognition. Our study sheds light on potential issues in the design and analysis of middle-aged biobank cohorts and underscores the need for caution when interpreting genetic association results based on proxy-reported parental disease history. Genetic associations based on parental history of Alzheimer’s disease are shown to be impacted by uncorrected survival bias and nonrandom survey participation, underscoring the need for caution when interpreting results based on this study design.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2696-2703"},"PeriodicalIF":31.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574513","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}

{"title":"Grapevine pangenome facilitates trait genetics and genomic breeding","authors":"Zhongjie Liu, Nan Wang, Ying Su, Qiming Long, Yanling Peng, Lingfei Shangguan, Fan Zhang, Shuo Cao, Xu Wang, Mengqing Ge, Hui Xue, Zhiyao Ma, Wenwen Liu, Xiaodong Xu, Chaochao Li, Xuejing Cao, Bilal Ahmad, Xiangnian Su, Yuting Liu, Guizhou Huang, Mengrui Du, Zhenya Liu, Yu Gan, Lei Sun, Xiucai Fan, Chuan Zhang, Haixia Zhong, Xiangpeng Leng, Yanhua Ren, Tianyu Dong, Dan Pei, Xinyu Wu, Zhongxin Jin, Yiwen Wang, Chonghuai Liu, Jinfeng Chen, Brandon Gaut, Sanwen Huang, Jinggui Fang, Hua Xiao, Yongfeng Zhou","doi":"10.1038/s41588-024-01967-5","DOIUrl":"10.1038/s41588-024-01967-5","url":null,"abstract":"Grapevine breeding is hindered by a limited understanding of the genetic basis of complex agronomic traits. This study constructs a graph-based pangenome reference (Grapepan v.1.0) from 18 newly generated phased telomere-to-telomere assemblies and 11 published assemblies. Using Grapepan v.1.0, we build a variation map with 9,105,787 short variations and 236,449 structural variations (SVs) from the resequencing data of 466 grapevine cultivars. Integrating SVs into a genome-wide association study, we map 148 quantitative trait loci for 29 agronomic traits (50.7% newly identified), with 12 traits significantly contributed by SVs. The estimated heritability improves by 22.78% on average when including SVs. We discovered quantitative trait locus regions under divergent artificial selection in metabolism and berry development between wine and table grapes, respectively. Moreover, significant genetic correlations were detected among the 29 traits. Under a polygenic model, we conducted genomic predictions for each trait. In general, our study facilitates the breeding of superior cultivars via the genomic selection of multiple traits. By constructing a graph-based grapevine pangenome reference (Grapepan v.1.0) and incorporating structural variations and phenotypic maps, the study investigates the genetic basis of agronomic traits, empowering grapevine genomic breeding.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2804-2814"},"PeriodicalIF":31.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01967-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Systematic assessment of ISWI subunits shows that NURF creates local accessibility for CTCF","authors":"Mario Iurlaro, Francesca Masoni, Ilya M. Flyamer, Christiane Wirbelauer, Murat Iskar, Lukas Burger, Luca Giorgetti, Dirk Schübeler","doi":"10.1038/s41588-024-01985-3","DOIUrl":"10.1038/s41588-024-01985-3","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2574-2575"},"PeriodicalIF":31.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01985-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Standardizing variant naming in literature with VariantValidator to increase diagnostic rates","authors":"Peter J. Freeman, John F. Wagstaff, Ivo F. A. C. Fokkema, Garry R. Cutting, Heidi L. Rehm, Angela C. Davies, Johan T. den Dunnen, Liam J. Gretton, Raymond Dalgleish","doi":"10.1038/s41588-024-02001-4","DOIUrl":"10.1038/s41588-024-02001-4","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2574-2574"},"PeriodicalIF":31.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02001-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convergence and divergence of diploid and tetraploid cotton genomes","authors":"Jianying Li, Zhenping Liu, Chunyuan You, Zhengyang Qi, Jiaqi You, Corrinne E. Grover, Yuexuan Long, Xianhui Huang, Sifan Lu, Yuejin Wang, Sainan Zhang, Yawen Wang, Ruizhe Bai, Mengke Zhang, Shuangxia Jin, Xinhui Nie, Jonathan F. Wendel, Xianlong Zhang, Maojun Wang","doi":"10.1038/s41588-024-01964-8","DOIUrl":"10.1038/s41588-024-01964-8","url":null,"abstract":"Polyploidy is an important driving force in speciation and evolution; however, the genomic basis for parallel selection of a particular trait between polyploids and ancestral diploids remains unexplored. Here we construct graph-based pan-genomes for diploid (A2) and allotetraploid (AD1) cotton species, enabled by an assembly of 50 genomes of genetically diverse accessions. We delineate a mosaic genome map of tetraploid cultivars that illustrates genomic contributions from semi-wild forms into modern cultivars. Pan-genome comparisons identify syntenic and hyper-divergent regions of continued variation between diploid and tetraploid cottons, and suggest an ongoing process of sequence evolution potentially linked to the contrasting genome size change in two subgenomes. We highlight 43% of genetic regulatory relationships for gene expression in diploid encompassing sequence divergence after polyploidy, and specifically characterize six underexplored convergent genetic loci contributing to parallel selection of fiber quality. This study offers a framework for pan-genomic dissection of genetic regulatory components underlying parallel selection of desirable traits in organisms. High-quality assemblies of 15 diploid and 35 allotetraploid cotton accessions are analyzed in graph-based pan-genomes, providing insights into genome dynamics and regulatory control of fiber transcriptomes under varying ploidy and selection pressures.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2562-2573"},"PeriodicalIF":31.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536626","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}

{"title":"Gene-based burden tests of rare germline variants identify six cancer susceptibility genes","authors":"Erna V. Ivarsdottir, Julius Gudmundsson, Vinicius Tragante, Gardar Sveinbjornsson, Snaedis Kristmundsdottir, Simon N. Stacey, Gisli H. Halldorsson, Magnus I. Magnusson, Asmundur Oddsson, G. Bragi Walters, Asgeir Sigurdsson, Saedis Saevarsdottir, Doruk Beyter, Gudmar Thorleifsson, Bjarni V. Halldorsson, Pall Melsted, Hreinn Stefansson, Ingileif Jonsdottir, Erik Sørensen, Ole B. Pedersen, Christian Erikstrup, Martin Bøgsted, Mette Pøhl, Andreas Røder, Hein Vincent Stroomberg, Ismail Gögenur, Jens Hillingsø, Stig E. Bojesen, Ulrik Lassen, Estrid Høgdall, Henrik Ullum, Søren Brunak, Sisse R. Ostrowski, DBDS Genomic Consortium, Ida Elken Sonderby, Oleksandr Frei, Srdjan Djurovic, Alexandra Havdahl, Pal Moller, Mev Dominguez-Valentin, Jan Haavik, Ole A. Andreassen, Eivind Hovig, Bjarni A. Agnarsson, Rafn Hilmarsson, Oskar Th. Johannsson, Trausti Valdimarsson, Steinn Jonsson, Pall H. Moller, Jon H. Olafsson, Bardur Sigurgeirsson, Jon G. Jonasson, Geir Tryggvason, Hilma Holm, Patrick Sulem, Thorunn Rafnar, Daniel F. Gudbjartsson, Kari Stefansson","doi":"10.1038/s41588-024-01966-6","DOIUrl":"10.1038/s41588-024-01966-6","url":null,"abstract":"Discovery of cancer risk variants in the sequence of the germline genome can shed light on carcinogenesis. Here we describe gene burden association analyses, aggregating rare missense and loss of function variants, at 22 cancer sites, including 130,991 cancer cases and 733,486 controls from Iceland, Norway and the United Kingdom. We identified four genes associated with increased cancer risk; the pro-apoptotic BIK for prostate cancer, the autophagy involved ATG12 for colorectal cancer, TG for thyroid cancer and CMTR2 for both lung cancer and cutaneous melanoma. Further, we found genes with rare variants that associate with decreased risk of cancer; AURKB for any cancer, irrespective of site, and PPP1R15A for breast cancer, suggesting that inhibition of PPP1R15A may be a preventive strategy for breast cancer. Our findings pinpoint several new cancer risk genes and emphasize autophagy, apoptosis and cell stress response as a focus point for developing new therapeutics. Burden testing in three large European ancestry cohorts identifies new risk genes for a number of common cancer types, including pan-cancer protective variants in AURKB and breast cancer protective variants in PPP1R15A.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2422-2433"},"PeriodicalIF":31.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536566","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}

{"title":"Obesity-dependent selection of driver mutations in cancer","authors":"Cerise Tang, Venise Jan Castillon, Michele Waters, Chris Fong, Tricia Park, Sonia Boscenco, Susie Kim, Kelly Pekala, Jian Carrot-Zhang, A. Ari Hakimi, Nikolaus Schultz, Irina Ostrovnaya, Alexander Gusev, Justin Jee, Ed Reznik","doi":"10.1038/s41588-024-01969-3","DOIUrl":"10.1038/s41588-024-01969-3","url":null,"abstract":"Obesity is a risk factor for cancer, but whether obesity is linked to specific genomic subtypes of cancer is unknown. We examined the relationship between obesity and tumor genotype in two clinicogenomic corpora. Obesity was associated with specific driver mutations in lung adenocarcinoma, endometrial carcinoma and cancers of unknown primaries, independent of clinical covariates, demographic factors and genetic ancestry. Obesity is therefore a driver of etiological heterogeneity in some cancers. Analysis of pan-cancer clinical genomic sequencing finds that body mass index associates with driver mutations in certain cancer types, including most prominently lung adenocarcinoma. Obesity may thus influence tumor genetics.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2318-2321"},"PeriodicalIF":31.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01969-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping drug resistance variants in cancer, one base at a time","authors":"","doi":"10.1038/s41588-024-01976-4","DOIUrl":"10.1038/s41588-024-01976-4","url":null,"abstract":"DNA variants arising in the genome of cancer cells are a major cause of therapy failure, but for most variants, their effects on drug response are unknown. Base-editing screens provide a systematic approach to uncover the functions of cancer variants at scale, which might help to inform the use of precision cancer therapies.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2308-2309"},"PeriodicalIF":31.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489209","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}