medRxiv - Genetic and Genomic Medicine最新文献_第5页

A Phenome-Wide Association Study (PheWAS) of Genetic Risk for C-Reactive Protein in Children of European Ancestry: Results From the ABCD Study 欧洲血统儿童 C-Reactive 蛋白遗传风险全表型关联研究 (PheWAS)：ABCD 研究的结果

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-31 DOI: 10.1101/2024.08.30.24312857

Sara A. Norton, Aaron J. Gorelik, Sarah E. Paul, Emma C. Johnson, David AA Baranger, Jayne L Siudzinski, Zhaolong Adrian Li, Erin Bondy, Hailey Modi, Nicole R. Karcher, Tamara Hershey, Alexander S. Hatoum, Arpana Agrawal, Ryan Bogdan

引用次数: 0

Deciphering causal relationships between cell type-specific genetic factors and brain imaging-derived phenotypes and disorders 破译细胞类型特异性遗传因子与脑成像衍生表型和疾病之间的因果关系

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-31 DOI: 10.1101/2024.08.30.24312836

Anyi Yang, Xingzhong Zhao, Yucheng T. Yang, Xing-Ming Zhao

{"title":"Deciphering causal relationships between cell type-specific genetic factors and brain imaging-derived phenotypes and disorders","authors":"Anyi Yang, Xingzhong Zhao, Yucheng T. Yang, Xing-Ming Zhao","doi":"10.1101/2024.08.30.24312836","DOIUrl":"https://doi.org/10.1101/2024.08.30.24312836","url":null,"abstract":"The integration of expression quantitative trait loci (eQTLs) and genome-wide association study (GWAS) findings to identify causal genes aids in elucidating the biological mechanisms and the discovery of potential drug targets underlying complex traits. This can be achieved by Mendelian randomization (MR), but to date, most MR studies investigating the contribution of genes to brain phenotypes have been conducted on heterogeneous brain tissues and not on specific cell types, thus limiting our knowledge at the cellular level. In this study, we employ a MR framework to infer cell type-specific causal relationships between gene expression and brain-associated complex traits, using eQTL data from eight cell types and large-scale GWASs of 123 imaging-derived phenotypes (IDPs) and 26 brain disorders and behaviors (DBs). Our analysis constructs a cell type-specific causal gene atlas for IDPs and DBs, which include 254 and 217 potential causal cell type-specific eQTL target genes (eGenes) for IDPs and DBs, respectively. The identified results exhibit high cell type specificity, with over 90% of gene-IDP and 80% of gene-DB associations being unique to a single cell type. We highlight shared cell type-specific patterns between IDPs and DBs, characterize the putative causal pathways among cell type-specific causal eGenes, DBs and IDPs, and reveal the spatiotemporal expression patterns of these cell type-specific causal eGenes. We also demonstrate that cell type-specific causal eGenes can characterize the associations between IDPs and DBs. In summary, our study provides novel insights into the genetic foundations at the cellular level that influence brain structures, disorders and behaviors, which reveals important implications for therapeutic targets and brain health management.","PeriodicalId":501375,"journal":{"name":"medRxiv - Genetic and Genomic Medicine","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improved characterization of gene-environment interactions for vitamin D through variance quantitative trait loci 通过方差数量性状位点改进维生素 D 基因与环境相互作用的特征描述

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-31 DOI: 10.1101/2024.08.30.24312868

Tianyuan Lu, Wenmin Zhang, Cassianne Robinson-Cohen, Corinne D. Engelman, Qiongshi Lu, Ian H. de Boer, Lei Sun, Andrew D. Paterson

引用次数: 0

Type 1 Diabetes Genetic Risk Score classifies diabetes subtypes in Indians: Impact of HLA diversity on the lower discriminative ability 1 型糖尿病遗传风险评分可对印度人的糖尿病亚型进行分类：HLA 多样性对较低分辨能力的影响

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-31 DOI: 10.1101/2024.08.31.24312873

Alagu Sankareswaran, Pooja Kunte, Diane P Fraser, Mobeen Shaik, Michael N Weedon, Richard A Oram, Chittaranjan S Yajnik, Giriraj R Chandak

引用次数: 0

Exome sequencing identifies ABCA7 as an important gene for familial AD cases from Eastern India 外显子组测序发现 ABCA7 是印度东部家族性注意力缺失症病例的重要基因

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-31 DOI: 10.1101/2024.08.30.24312765

Dipanwita Sadhukhan, Adreesh Mukherjee, Bidisha Bhattacharyya, Smriti Mishra, Tapas Kumar Banerjee, Gautam Das, Uma Sinharoy, Subhra Prakash Hui, Soma Gupta, Atanu Biswas, Arindam Biswas

引用次数: 0

Resolving the diagnostic odyssey in inherited retinal dystrophies through long-read genome sequencing 通过长线程基因组测序解决遗传性视网膜营养不良症的诊断难题

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-30 DOI: 10.1101/2024.08.28.24312668

Gerardo Fabian-Morales, Vianey Ordoñez-Labastida, William J. Rowell, Christine Lambert, Cairbre Fanslow, Alexander Robertson, Juan C. Zenteno

引用次数: 0

cfGWAS reveal genetic basis of cell-free DNA features cfGWAS 揭示无细胞 DNA 特征的遗传基础

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-30 DOI: 10.1101/2024.08.28.24312755

Huanhuan Zhu, Yan Zhang, Shuang Zeng, Linxuan Li, Rijing Ou, Xinyi Zhang, Yu Lin, Ying Lin, Chuang Xu, Lin Wang, Guodan Zeng, Jingyu Zeng, Lingguo Li, Yongjian Jia, Yu Wang, Fei Luo, Meng Yang, Yuxuan Hu, Xiameizi Li, Han Xiao, Xun Xu, Jian Wang, Aifen Zhou, Haiqiang Zhang, Xin Jin

{"title":"cfGWAS reveal genetic basis of cell-free DNA features","authors":"Huanhuan Zhu, Yan Zhang, Shuang Zeng, Linxuan Li, Rijing Ou, Xinyi Zhang, Yu Lin, Ying Lin, Chuang Xu, Lin Wang, Guodan Zeng, Jingyu Zeng, Lingguo Li, Yongjian Jia, Yu Wang, Fei Luo, Meng Yang, Yuxuan Hu, Xiameizi Li, Han Xiao, Xun Xu, Jian Wang, Aifen Zhou, Haiqiang Zhang, Xin Jin","doi":"10.1101/2024.08.28.24312755","DOIUrl":"https://doi.org/10.1101/2024.08.28.24312755","url":null,"abstract":"cfDNA consists of degraded DNA fragments released into body fluids. Its genetic and pathological information makes it useful for prenatal testing and early tumor detection. However, the mechanisms behind cfDNA biology are largely unknown. In this study, for the first time, we conducted a GWAS study to explore the genetic basis of cfDNA features, termed cfGWAS, in 28,016 pregnant women. We identified 84 significant loci, including well-known cfDNA-related genes DFFB and DNASE1L3, and numerous novel genes potentially involved in cfDNA biology, including PANX1 and DNASE1L1. The findings were further verified through independent GWAS and experimental validation in knockout mice and cell lines. Subsequent analyses revealed strong causal relationships of hematological indicators on cfDNA features. In summary, we presented the first cfGWAS, revealing the genetic basis of cfDNA biology from genome-wide scale. Novel knowledge uncovered by this study keep the promise to revolutionize liquid biopsy technology and potential new drug targeted for certain disease. Given exist of the millions cfDNA whole-genome-sequencing data generated from clinical testing, the potential of this paradigm is enormous.","PeriodicalId":501375,"journal":{"name":"medRxiv - Genetic and Genomic Medicine","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient molecular mendelian randomization screens with LaScaMolMR.jl 利用 LaScaMolMR.jl 进行高效分子泯灭随机筛选

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-30 DOI: 10.1101/2024.08.29.24312805

Samuel Mathieu, Louis-Hippolyte Minvielle Moncla, Mewen Briend, Valentine Duclos, Anne Rufiange, Yohan Bossé, Patrick Mathieu

{"title":"Efficient molecular mendelian randomization screens with LaScaMolMR.jl","authors":"Samuel Mathieu, Louis-Hippolyte Minvielle Moncla, Mewen Briend, Valentine Duclos, Anne Rufiange, Yohan Bossé, Patrick Mathieu","doi":"10.1101/2024.08.29.24312805","DOIUrl":"https://doi.org/10.1101/2024.08.29.24312805","url":null,"abstract":"<strong>Summary</strong> The ever-growing genetic cohorts lead to an increase in scale of molecular Quantitative Trait Loci (QTL) studies, creating opportunities for more extensive two samples Mendelian randomization (MR) investigations aiming to identify causal relationships between molecular traits and diseases. This increase led to the identification of multiple causal candidates and potential drug targets over time. However, the increase in scale of such studies and higher dimension multi-omic data come with computational challenges. We present “LArge SCAle MOLecular Mendelian Randomization with Julia” (LaScaMolMR.jl), an open-sourced integrated Julia package optimized for Omic-wide Mendelian Randomization (OWMR) Studies. This versatile package eliminates the two-language problem and implements fast algorithms for instrumental variable selection approaches with both cis and trans instruments and performs the most popular regression estimators for MR studies with molecular exposures. It reduces the compute time via meta-programming allowing easy deployment of multi-threaded approach and the internalization of linkage disequilibrium investigation of potential instrumental variables. Via its integrated approach and high-computational performance, LaScaMolMR.jl allows users who have minimal programming experience to perform large scale OWMR studies.","PeriodicalId":501375,"journal":{"name":"medRxiv - Genetic and Genomic Medicine","volume":"131 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endogamy and high prevalence of deleterious mutations in India: evidence from strong founder events 印度的内交配和高流行率的有害突变：来自强创始人事件的证据

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-29 DOI: 10.1101/2024.08.21.24312342

Pratheusa Machha, Amirtha Gopalan, Yamini Elangovan, Sarath Chandra Mouli Veeravalli, Divya Tej Sowpati, Kumarasamy Thangaraj

{"title":"Endogamy and high prevalence of deleterious mutations in India: evidence from strong founder events","authors":"Pratheusa Machha, Amirtha Gopalan, Yamini Elangovan, Sarath Chandra Mouli Veeravalli, Divya Tej Sowpati, Kumarasamy Thangaraj","doi":"10.1101/2024.08.21.24312342","DOIUrl":"https://doi.org/10.1101/2024.08.21.24312342","url":null,"abstract":"Founder events influence recessive diseases in highly endogamous populations. Several Indian populations have experienced significant founder events and maintained strict endogamy. Genomic studies in Indian populations often lack in addressing clinical implications of these phenomena. We performed whole-exome sequencing of 281 individuals from four South Indian groups to evaluate population-specific disease causing mutations associated with founder events. Our study revealed a high inbreeding rate of 59% across the groups. We identified ∼29.2% of the variants to be exclusive to a single population and uncovered 1,284 novel exonic variants, underscoring the genetic underrepresentation of Indian populations. Among these, 23 predicted as deleterious were found in heterozygous state, suggesting they may be pathogenic in a homozygous state and are common in the endogamous groups. Approximately 40-68% of the identified pathogenic variants showed significantly higher occurrence rates. Pharmacogenomic analysis revealed distinct allele frequencies in CYP450 and non-CYP450 gene variants, highlighting heterogeneous drug responses and associated risks. We report a high prevalence of ankylosing spondylitis in Reddys, linked to <em>HLA-B*27:04</em> allele and strong founder effect. Our findings emphasize the need for expanded genomic research in understudied Indian populations to elucidate disease risk and medical profiles, eventually aiming towards precision medicine and mitigating disease burden.","PeriodicalId":501375,"journal":{"name":"medRxiv - Genetic and Genomic Medicine","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulatory variation at serotonin receptor 1F (HTR1F) modulates arousals and risk for sleep apnea 血清素受体 1F (HTR1F) 的调节变异可调节唤醒和睡眠呼吸暂停的风险

medRxiv - Genetic and Genomic Medicine Pub Date : 2024-08-29 DOI: 10.1101/2024.08.29.24312459

Satu Strausz, Martin Broberg, Samuel E Jones, Jukka Koskela, Tuomo Kiiskinen, FinnGen, Aarno Palotie, Tuula Palotie, Adel Bachour, Richa Saxena, Samuli Ripatti, Erik Abner, Hanna M. Ollila

引用次数: 0