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Improved methods for multi-trait fine mapping of pleiotropic risk loci [article]

Gleb Kichaev, Megan Roytman, Ruth Johnson, Eleazar Eskin, Sara Lindstroem, Peter Kraft, Bogdan Pasaniuc
2016 bioRxiv   pre-print
Next, we show that jointly modeling pleiotropic risk regions improves fine-mapping resolution compared to standard single trait and pleiotropic fine mapping strategies.  ...  In this work we introduce a new approach, fastPAINTOR, that leverages evidence across correlated traits, as well as functional annotation data, to improve fine-mapping accuracy at pleiotropic risk loci  ...  The power of our multi-trait fine-mapping framework hinges on the assumption that causal variants are shared at pleiotropic risk regions.  ... 
doi:10.1101/054684 fatcat:pp7idrzfazg5ra532xw22kccoy

Improved methods for multi-trait fine mapping of pleiotropic risk loci

Gleb Kichaev, Megan Roytman, Ruth Johnson, Eleazar Eskin, Sara Lindström, Peter Kraft, Bogdan Pasaniuc
2016 Bioinformatics  
fastPAINTOR, that leverages evidence across correlated traits, as well as functional annotation data, to improve fine-mapping accuracy at pleiotropic risk loci.  ...  Next, we show that jointly modeling pleiotropic risk regions improves fine-mapping resolution relative to standard single trait and pleiotropic fine mapping strategies.  ...  The power of our multi-trait fine-mapping framework hinges on the assumption that causal variants are shared at pleiotropic risk regions.  ... 
doi:10.1093/bioinformatics/btw615 pmid:27663501 pmcid:PMC5254076 fatcat:w5sbazxqmvgjfmfpa35ji66oqu

Analysis across Taiwan Biobank, Biobank Japan and UK Biobank identifies hundreds of novel loci for 36 quantitative traits [article]

Chia-Yen Chen, Tzu-Ting Chen, Yen-Chen Anne Feng, Ryan J. Longchamps, Shu-Chin Lin, Shi-Heng Wang, Yi-Hsiang Hsu, Hwai-I Yang, Po-Hsiu Kuo, Mark J. Daly, Wei J. Chen, Hailiang Huang (+2 others)
2021 medRxiv   pre-print
Genome-wide association studies (GWAS) have identified tens of thousands of genetic loci associated with human complex traits and diseases.  ...  We release all GWAS summary statistics, fine-mapping results, and single nucleotide polymorphism (SNP) weights and TWB-based PRS reference distributions for polygenic prediction (link to appear upon publication  ...  We thank the National Center for Genome Medicine of Taiwan for the technical support in genotyping.  ... 
doi:10.1101/2021.04.12.21255236 fatcat:c6nbdkzmsfeohfxgwn7usc6f4u

Identification of novel variants associated with osteoporosis, type 2 diabetes and potentially pleiotropic loci using pleiotropic cFDR method

Yuan Hu, Li-Jun Tan, Xiang-Ding Chen, Jonathan Greenbaum, Hong-Wen Deng
2018 Bone  
The aim of this study was to identify novel genetic variants for osteoporosis and/or T2D.  ...  However, the total genetic variance for each of these two diseases and the shared genetic determination between them are largely unknown.  ...  Ecology (0713) and the Cooperative Innovation Center of Engineering and New Products for Developmental Biology of Hunan Province (20134486).  ... 
doi:10.1016/j.bone.2018.08.020 pmid:30172742 pmcid:PMC6364698 fatcat:svom4u2sy5devh2jz3xyhb7gqu

Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett's oesophagus and provides insights into clinical heterogeneity in reflux diagnosis

Jue-Sheng Ong, Jiyuan An, Xikun Han, Matthew H Law, Priyanka Nandakumar, Johannes Schumacher, Ines Gockel, Anne Bohmer, Janusz Jankowski, Claire Palles, Catherine M Olsen, Rachel E Neale (+10 others)
2021 Gut  
multitrait model identified many novel risk loci for GERD and BE.  ...  We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven  ...  We finally also thank the 23andMe staff members and 23andMe research participants for generating the replication data in this publication.  ... 
doi:10.1136/gutjnl-2020-323906 pmid:34187846 fatcat:24dyguatpjevroazd3fjbmyhne

A global view of pleiotropy and genetic architecture in complex traits [article]

Kyoko Watanabe, Sven Stringer, Oleksandr Frei, Masa Umićević Mirkov, Tinca J.C. Polderman, Sophie van der Sluis, Ole A. Andreassen, Benjamin M. Neale, Danielle Posthuma
2018 bioRxiv   pre-print
We show that trait associated loci cover more than half of the genome, and 90% of those loci are associated with multiple trait domains.  ...  For a subset of well-powered GWAS on 558 unique traits, we provide an extensive overview of pleiotropy and genetic architecture.  ...  region to fine-map by taking 50kb around the top SNPs of the trait-associated 780 loci.  ... 
doi:10.1101/500090 fatcat:77gtykmhvzen3lh5rviqfycl4a

Genome wide association study of body weight, body mass index, adiposity, and fasting glucose in 3,173 outbred rats [article]

Apurva S. Chitre, Oksana Polesskaya, Katie Holl, Jianjun Gao, Riyan Cheng, Angel Garcia Martinez, Tony George, Alexander F. Gileta, Wenyan Han, Aidan Horvath, Alesa Hughson, Keita Ishiwari (+15 others)
2018 bioRxiv   pre-print
Highly recombinant populations allow for genetic fine-mapping of complex traits, greatly reducing the number of plausible candidate genes.  ...  Our results demonstrate the potential for rodent studies to add to our understanding of the molecular genetic factors that contribute to obesity-relevant traits and emphasize the importance of sample size  ...  This work demonstrates the power of HS rats for fine-mapping and gene identification of adiposity traits, including the power to identify genetic loci across multiple institutions and environmental influence  ... 
doi:10.1101/422428 fatcat:yfungx7p3ffpphg56uceuj3cyy

Genetic associations at regulatory phenotypes improve fine-mapping of causal variants for twelve immune-mediated diseases [article]

Kousik Kundu, Alice L. Mann, Manuel Tardaguila, Stephen Watt, Hannes Ponstingl, Louella Vasquez, Nicholas W. Morrell, Oliver Stegle, Tomi Pastinen, Stephen J. Sawcer, Carl A. Anderson, Klaudia Walter (+1 others)
2020 bioRxiv   pre-print
Here we use data from the BLUEPRINT project to identify regulatory quantitative trait loci (QTL) for three primary human immune cell types and use these to fine-map putative causal variants for twelve  ...  The identification of causal genetic variants for common diseases improves understanding of disease biology.  ...  We thank Lu Chen and Valentina Iotchkova for the initial technical discussion on analysis strategy, and Katrina M de Lange for helping with IBD GWAS data.  ... 
doi:10.1101/2020.01.15.907436 fatcat:tzt5tr4ulvhnfdxouwv2mysjxm

Dissecting the genetics of complex traits using summary association statistics [article]

Bogdan Pasaniuc, Alkes L Price
2016 bioRxiv   pre-print
These studies have produced vast repositories of genetic variation and trait measurements across millions of individuals, providing tremendous opportunities for further analyses.  ...  Here we review recent progress on statistical methods that leverage summary association data to gain insights into the genetic basis of complex traits and diseases.  ...  Shi for helpful discussions. We are grateful to G. Kichaev and R. Johnson for help with Figure 3 . This work was funded by NIH grants R01 HG006399, R01 MH101244, R01 GM105857 and R01 MH107649.  ... 
doi:10.1101/072934 fatcat:c7onk6qsrjd5zj2aa3izbzly4q

The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers

Christopher I. Amos, Joe Dennis, Zhaoming Wang, Jinyoung Byun, Fredrick R. Schumacher, Simon A. Gayther, Graham Casey, David J. Hunter, Thomas A. Sellers, Stephen B. Gruber, Alison M. Dunning, Kyriaki Michailidou (+81 others)
2016 Cancer Epidemiology, Biomarkers and Prevention  
the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for diseasespecific risk, and jointly model genetic, environmental, and lifestyle-related exposures.  ...  Conclusions: Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess  ...  Moss for his help in organizing this manuscript submission. Grant Support  ... 
doi:10.1158/1055-9965.epi-16-0106 pmid:27697780 pmcid:PMC5224974 fatcat:ero45y2p7bawjml7wryqkvaqqm

Investigating asthma heterogeneity through shared and distinct genetics: insights from genome-wide cross-trait analysis

Zhaozhong Zhu, Kohei Hasegawa, Carlos A. Camargo, Liming Liang
2020 Journal of Allergy and Clinical Immunology  
We also make recommendations for future directions: 1) ethnicity-specific asthma GWASs, and 2) application of cross-trait methods to multi-omics data to dissect the heritability found in GWAS.  ...  The genome-wide cross-trait analysis features in several analytical aspects: genetic correlation, cross-trait meta-analysis, Mendelian randomization, polygenic risk score and functional analysis.  ...  region are difficult to map in fine resolution.  ... 
doi:10.1016/j.jaci.2020.07.004 pmid:32693092 pmcid:PMC7368660 fatcat:jmiujfjxubhbdhcnfz5zanqz6u

Integrative analysis of genome-wide association studies identifies novel loci associated with neuropsychiatric disorders

Xueming Yao, Joseph T. Glessner, Junyi Li, Xiaohui Qi, Xiaoyuan Hou, Chonggui Zhu, Xiaoge Li, Michael E. March, Liu Yang, Frank D. Mentch, Heather S. Hain, Xinyi Meng (+3 others)
2021 Translational Psychiatry  
In the multi-trait joint analyses, we found five novel genome-wide significant loci for ADHD, one novel locus for BIP, and ten novel loci for MDD.  ...  We conducted fine-mapping and functional annotation through an integrative multi-omics approach and identified causal variants and potential target genes at each novel locus.  ...  for Applied Genomics at CHOP.  ... 
doi:10.1038/s41398-020-01195-5 pmid:33479212 pmcid:PMC7820351 fatcat:ts2ylwpmgrh3fc4nlvbmtntwzy

48th European Mathematical Genetics Meeting (EMGM) 2020

Zoltan Kutalik
2020 Human Heredity  
While many methods have been proposed in literature for the detection of pleiotropic locus, their applicability is to a large extent defined by the type of data available and their relative performance  ...  Local gene expression quantitative trait loci (cis-eQTLs) regularly implicate multiple putative target genes whose disease relevance and function is often poorly understood.  ...  Using summary statistics, flashfm (FLexible And SHared information Fine-Mapping) fine-maps association signals for multiple quantitative traits, allowing for missing trait measurements and related individuals  ... 
doi:10.1159/000507248 pmid:32268327 fatcat:3aneluafpnes3a2ayzn53uffca

Integrated Analysis of Summary Statistics to Identify Pleiotropic Genes and Pathways for the Comorbidity of Schizophrenia and Cardiometabolic Disease

Hao Liu, Yang Sun, Xinxin Zhang, Shiyang Li, Dong Hu, Lei Xiao, Yanghui Chen, Lin He, Dao Wen Wang
2020 Frontiers in Psychiatry  
Here we integrated comprehensive multi-dimensional data from GWAS, expression quantitative trait loci (eQTL), and gene set database to systematically identify potential pleiotropic genes and biological  ...  Our study provides insights into the pleiotropic genes and biological pathways underlying mechanisms for the comorbidity of SCZ and CMD.  ...  Dao Wen Wang for their cultivation and learning support.  ... 
doi:10.3389/fpsyt.2020.00256 pmid:32425817 pmcid:PMC7212438 fatcat:c7shqaidyve6vfftdhemta6m2y

Integrative Analyses Reveal Novel Disease-associated Loci and Genes for Idiopathic Pulmonary Fibrosis [article]

Ming Chen, Yiliang Zhang, Taylor S. Adams, Dingjue Ji, Wei Jiang, Louise V. Wain, Michael H. Cho, Naftali Kaminski, Hongyu Zhao
2021 medRxiv   pre-print
Methods: By leveraging shared genetic information and transcriptome data, we conducted an integrative analysis to identify novel genes for IPF.  ...  We first considered observed phenotypes, polygenic risk scores, and genetic correlations to investigate associations between IPF and other traits in the UK Biobank.  ...  These findings motivated us to further fine-map local pleiotropic effects and find candidate pleiotropic genes.  ... 
doi:10.1101/2021.05.11.21257064 fatcat:oyjtngvitnc4dhsxhpi6x5qg74
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