ORCID Profile
0000-0002-4758-9081
Current Organisations
University of Oxford
,
Oxford University Hospitals NHS Trust
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Publisher: Springer Science and Business Media LLC
Date: 31-05-2018
DOI: 10.1038/S42003-018-0052-4
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 .
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2019
DOI: 10.1097/BPO.0000000000001318
Abstract: Children with cerebral palsy are at risk for progressive hip displacement. Since surveillance for hip displacement uses specific radiographic measurements to guide decision making, it is important to establish the reliability of these measurements, which include Reimer’s migration percentage (MP), acetabular index or acetabular angle (AI or AA), and pelvic obliquity (PO). The purpose of this study was to determine the intraobserver and interobserver reliability of these radiographic measures among an international group of pediatric orthopaedic surgeons participating in the prospective international multicenter Cerebral Palsy Hip Outcomes Project (CHOP) currently underway to evaluate the outcomes of hip interventions in cerebral palsy. Two compact discs (CDs) containing the same 25 anteroposterior pelvis radiographs in Digital Imaging and Communications in Medicine (DICOM) format were provided to participating surgeons at least 2 weeks apart. To reduce the likelihood of recall or any effects of learning or fatigue, the order of the radiographs varied on the 2 CD versions, and participating surgeons received the 2 CDs in random order. The intraclass correlation coefficients (ICCs) were calculated to assess interobserver and intraobserver reliability. Mean absolute differences of hip measurements obtained at 2 time points were also calculated. The MP had the highest reliability followed by PO, AI, and AA with a mean intrarater ICC (SD range) of 0.95 (0.04 0.84 to 0.98) 0.92 (0.03 0.85 to 0.97) 0.84 (0.05 0.75 to 0.92) and 0.82 (0.14 0.51 to 0.98) respectively. The mean interrater ICC (SD range) for MP, PO, AI, and AA were 0.94 (0.05 0.78 to 0.99) 0.90 (0.04 0.76 to 0.99) 0.79 (0.08 0.52 to 0.93) and 0.69 (0.23 0.42 to 0.98) for MP, PO, AI, and AA, respectively. The mean (SD 95% confidence interval) for the absolute difference between the 2 measurements for the raters was 4.9% (2.9% 3.4%-6.4%) 3. 8 degrees (1.2 degrees 3.1-4.5 degrees) 2.6 degrees (1.5 degrees 1.7-3.5 degrees) and 1.3 degrees (0.3 degrees 1.29-1.31 degrees) for MP, AI, AA, and PO, respectively. MP is a reproducible measure with excellent intrarater and interrater reliability. However, differences in MP of % should be treated with caution as these might be a consequence of measurement error. Although we found a high level of intrarater and interrater reliability of the AI, AA, and PO, these measurements are more variable and not ideal for use as discrete outcome measures. Instead, these parameters might be useful for prognostication and decision making when consistent trends are observed longitudinally over time which might be better indications of true change.
Location: No location found
Location: Greece
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Tim Theologis.