M K Sobczyk1, T R Gaunt1, L Paternoster1. 1. MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK.
Abstract
MOTIVATION: Gene prioritization at human GWAS loci is challenging due to linkage-disequilibrium and long-range gene regulatory mechanisms. However, identifying the causal gene is crucial to enable identification of potential drug targets and better understanding of molecular mechanisms. Mapping GWAS traits to known phenotypically relevant Mendelian disease genes near a locus is a promising approach to gene prioritization. RESULTS: We present MendelVar, a comprehensive tool that integrates knowledge from four databases on Mendelian disease genes with enrichment testing for a range of associated functional annotations such as Human Phenotype Ontology, Disease Ontology and variants from ClinVar. This open web-based platform enables users to strengthen the case for causal importance of phenotypically matched candidate genes at GWAS loci. We demonstrate the use of MendelVar in post-GWAS gene annotation for type 1 diabetes, type 2 diabetes, blood lipids and atopic dermatitis. AVAILABILITY AND IMPLEMENTATION: MendelVar is freely available at https://mendelvar.mrcieu.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: Gene prioritization at human GWAS loci is challenging due to linkage-disequilibrium and long-range gene regulatory mechanisms. However, identifying the causal gene is crucial to enable identification of potential drug targets and better understanding of molecular mechanisms. Mapping GWAS traits to known phenotypically relevant Mendelian disease genes near a locus is a promising approach to gene prioritization. RESULTS: We present MendelVar, a comprehensive tool that integrates knowledge from four databases on Mendelian disease genes with enrichment testing for a range of associated functional annotations such as Human Phenotype Ontology, Disease Ontology and variants from ClinVar. This open web-based platform enables users to strengthen the case for causal importance of phenotypically matched candidate genes at GWAS loci. We demonstrate the use of MendelVar in post-GWAS gene annotation for type 1 diabetes, type 2 diabetes, blood lipids and atopic dermatitis. AVAILABILITY AND IMPLEMENTATION: MendelVar is freely available at https://mendelvar.mrcieu.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Malika Kumar Freund; Kathryn S Burch; Huwenbo Shi; Nicholas Mancuso; Gleb Kichaev; Kristina M Garske; David Z Pan; Zong Miao; Karen L Mohlke; Markku Laakso; Päivi Pajukanta; Bogdan Pasaniuc; Valerie A Arboleda Journal: Am J Hum Genet Date: 2018-10-04 Impact factor: 11.025
Authors: T Agner; K Aalto-Korte; K E Andersen; C Foti; A Gimenéz-Arnau; M Goncalo; A Goossens; C Le Coz; T L Diepgen Journal: J Eur Acad Dermatol Venereol Date: 2015-09-15 Impact factor: 6.166
Authors: Helen V Firth; Shola M Richards; A Paul Bevan; Stephen Clayton; Manuel Corpas; Diana Rajan; Steven Van Vooren; Yves Moreau; Roger M Pettett; Nigel P Carter Journal: Am J Hum Genet Date: 2009-04-02 Impact factor: 11.025
Authors: Maxim V Kuleshov; Matthew R Jones; Andrew D Rouillard; Nicolas F Fernandez; Qiaonan Duan; Zichen Wang; Simon Koplev; Sherry L Jenkins; Kathleen M Jagodnik; Alexander Lachmann; Michael G McDermott; Caroline D Monteiro; Gregory W Gundersen; Avi Ma'ayan Journal: Nucleic Acids Res Date: 2016-05-03 Impact factor: 16.971
Authors: Yao Hu; Mariaelisa Graff; Jeffrey Haessler; Steven Buyske; Stephanie A Bien; Ran Tao; Heather M Highland; Katherine K Nishimura; Niha Zubair; Yingchang Lu; Marie Verbanck; Austin T Hilliard; Derek Klarin; Scott M Damrauer; Yuk-Lam Ho; Peter W F Wilson; Kyong-Mi Chang; Philip S Tsao; Kelly Cho; Christopher J O'Donnell; Themistocles L Assimes; Lauren E Petty; Jennifer E Below; Ozan Dikilitas; Daniel J Schaid; Matthew L Kosel; Iftikhar J Kullo; Laura J Rasmussen-Torvik; Gail P Jarvik; Qiping Feng; Wei-Qi Wei; Eric B Larson; Frank D Mentch; Berta Almoguera; Patrick M Sleiman; Laura M Raffield; Adolfo Correa; Lisa W Martin; Martha Daviglus; Tara C Matise; Jose Luis Ambite; Christopher S Carlson; Ron Do; Ruth J F Loos; Lynne R Wilkens; Loic Le Marchand; Chris Haiman; Daniel O Stram; Lucia A Hindorff; Kari E North; Charles Kooperberg; Iona Cheng; Ulrike Peters Journal: PLoS Genet Date: 2020-03-30 Impact factor: 5.917
Authors: Edward Mountjoy; Ellen M Schmidt; Miguel Carmona; Jeremy Schwartzentruber; Gareth Peat; Alfredo Miranda; Luca Fumis; James Hayhurst; Annalisa Buniello; Mohd Anisul Karim; Daniel Wright; Andrew Hercules; Eliseo Papa; Eric B Fauman; Jeffrey C Barrett; John A Todd; David Ochoa; Ian Dunham; Maya Ghoussaini Journal: Nat Genet Date: 2021-10-28 Impact factor: 38.330
Authors: Douglas P Kiel; John P Kemp; Fernando Rivadeneira; Jennifer J Westendorf; David Karasik; Emma L Duncan; Yuuki Imai; Ralph Müller; Jason Flannick; Lynda Bonewald; Noël Burtt Journal: J Bone Miner Res Date: 2020-09 Impact factor: 6.741
Authors: Daniel L McCartney; Josine L Min; Rebecca C Richmond; Ake T Lu; Maria K Sobczyk; Gail Davies; Linda Broer; Xiuqing Guo; Ayoung Jeong; Jeesun Jung; Silva Kasela; Seyma Katrinli; Pei-Lun Kuo; Pamela R Matias-Garcia; Pashupati P Mishra; Marianne Nygaard; Teemu Palviainen; Amit Patki; Laura M Raffield; Scott M Ratliff; Tom G Richardson; Oliver Robinson; Mette Soerensen; Dianjianyi Sun; Pei-Chien Tsai; Matthijs D van der Zee; Rosie M Walker; Xiaochuan Wang; Yunzhang Wang; Rui Xia; Zongli Xu; Jie Yao; Wei Zhao; Steve Horvath; Riccardo E Marioni; Adolfo Correa; Eric Boerwinkle; Pierre-Antoine Dugué; Peter Durda; Hannah R Elliott; Christian Gieger; Eco J C de Geus; Sarah E Harris; Gibran Hemani; Medea Imboden; Mika Kähönen; Sharon L R Kardia; Jacob K Kresovich; Shengxu Li; Kathryn L Lunetta; Massimo Mangino; Dan Mason; Andrew M McIntosh; Jonas Mengel-From; Ann Zenobia Moore; Joanne M Murabito; Miina Ollikainen; James S Pankow; Nancy L Pedersen; Annette Peters; Silvia Polidoro; David J Porteous; Olli Raitakari; Stephen S Rich; Dale P Sandler; Elina Sillanpää; Alicia K Smith; Melissa C Southey; Konstantin Strauch; Hemant Tiwari; Toshiko Tanaka; Therese Tillin; Andre G Uitterlinden; David J Van Den Berg; Jenny van Dongen; James G Wilson; John Wright; Idil Yet; Donna Arnett; Stefania Bandinelli; Jordana T Bell; Alexandra M Binder; Dorret I Boomsma; Wei Chen; Kaare Christensen; Karen N Conneely; Paul Elliott; Luigi Ferrucci; Myriam Fornage; Sara Hägg; Caroline Hayward; Marguerite Irvin; Jaakko Kaprio; Deborah A Lawlor; Terho Lehtimäki; Falk W Lohoff; Lili Milani; Roger L Milne; Nicole Probst-Hensch; Alex P Reiner; Beate Ritz; Jerome I Rotter; Jennifer A Smith; Jack A Taylor; Joyce B J van Meurs; Paolo Vineis; Melanie Waldenberger; Ian J Deary; Caroline L Relton Journal: Genome Biol Date: 2021-06-29 Impact factor: 17.906