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Genome-wide association study of developmental dysplasia of the hip identifies an association with GDF5

Hatzikotoulas, K; Roposch, A; DDH Case Control Consortium, .; Shah, KM; Clark, MJ; Bratherton, S; Limbani, V; ... Wilkinson, JM; + view all (2018) Genome-wide association study of developmental dysplasia of the hip identifies an association with GDF5. Communications Biology , 1 , Article 56. 10.1038/s42003-018-0052-4. Green open access

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Abstract

Developmental dysplasia of the hip (DDH) is the most common skeletal developmental disease. However, its genetic architecture is poorly understood. We conduct the largest DDH genome-wide association study to date and replicate our findings in independent cohorts. We find the heritable component of DDH attributable to common genetic variants to be 55% and distributed equally across the autosomal and X-chromosomes. We identify replicating evidence for association between GDF5 promoter variation and DDH (rs143384, effect allele A, odds ratio 1.44, 95% confidence interval 1.34–1.56, P = 3.55 × 10^{-22}). Gene-based analysis implicates GDF5 (P = 9.24 × 10^{-12}), UQCC1 (P = 1.86 × 10^{-10}), MMP24 (P = 3.18 × 10^{-9}), RETSAT (P = 3.70 × 10^{-8}) and PDRG1 (P = 1.06 × 10^{-7}) in DDH susceptibility. We find shared genetic architecture between DDH and hip osteoarthritis, but no predictive power of osteoarthritis polygenic risk score on DDH status, underscoring the complex nature of the two traits. We report a scalable, time-efficient recruitment strategy and establish for the first time to our knowledge a robust DDH genetic association locus at GDF5.

Type: Article
Title: Genome-wide association study of developmental dysplasia of the hip identifies an association with GDF5
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s42003-018-0052-4
Publisher version: https://doi.org/10.1038/s42003-018-0052-4
Language: English
Additional information: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Genome-wide association studies, Musculoskeletal abnormalities, Osteoarthritis, Population genetics
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10082354
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