Your browser doesn't support javascript.
loading
Influence of autozygosity on common disease risk across the phenotypic spectrum.
Malawsky, Daniel S; van Walree, Eva; Jacobs, Benjamin M; Heng, Teng Hiang; Huang, Qin Qin; Sabir, Ataf H; Rahman, Saadia; Sharif, Saghira Malik; Khan, Ahsan; Mirkov, Masa Umicevic; Kuwahara, Hiroyuki; Gao, Xin; Alkuraya, Fowzan S; Posthuma, Danielle; Newman, William G; Griffiths, Christopher J; Mathur, Rohini; van Heel, David A; Finer, Sarah; O'Connell, Jared; Martin, Hilary C.
Afiliación
  • Malawsky DS; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. Electronic address: dm22@sanger.ac.uk.
  • van Walree E; Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Complex Trait Genetics Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the Netherlands.
  • Jacobs BM; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
  • Heng TH; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Huang QQ; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Sabir AH; West Midlands Regional Clinical Genetics Unit, Birmingham Women's and Children's NHS FT, Birmingham, UK; Institute of Cancer and Genomics, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
  • Rahman S; Queen Square Institute of Neurology, University College London, London, UK.
  • Sharif SM; Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
  • Khan A; Waltham Forest Council, Waltham Forest Town Hall, Forest Road, Walthamstow E17 4JF, UK.
  • Mirkov MU; Congenica Limited, BioData Innovation Centre, Wellcome Genome Campus, Hinxton, UK.
  • Kuwahara H; King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Thuwal 23955, Saudi Arabia.
  • Gao X; King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Thuwal 23955, Saudi Arabia.
  • Alkuraya FS; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • Posthuma D; Department of Complex Trait Genetics Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the Netherlands.
  • Newman WG; Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Human Sciences, University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
  • Griffiths CJ; Wolfson Institute of Population Health, Queen Mary University of London, London, UK; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
  • Mathur R; Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
  • van Heel DA; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Finer S; Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
  • O'Connell J; 23andMe, Inc., Sunnyvale, CA, USA.
  • Martin HC; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. Electronic address: hcm@sanger.ac.uk.
Cell ; 186(21): 4514-4527.e14, 2023 10 12.
Article en En | MEDLINE | ID: mdl-37757828
Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (FROH) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of FROH. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between FROH and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Consanguinidad / Diabetes Mellitus Tipo 2 Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Humans País/Región como asunto: Europa Idioma: En Revista: Cell Año: 2023 Tipo del documento: Article
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Consanguinidad / Diabetes Mellitus Tipo 2 Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Humans País/Región como asunto: Europa Idioma: En Revista: Cell Año: 2023 Tipo del documento: Article