The identification of distinct protective and susceptibility mechanisms for hip osteoarthritis: findings from a genome-wide association study meta-analysis of minimum joint space width and Mendelian randomisation cluster analyses.

BACKGROUND: Hip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and (ii) identify which mJSW loci convey hip osteoarthritis (HOA) risk and would therefore be of therapeutic interest. METHODS: GWAS meta-analysis of hip mJSW derived from plain X-rays and DXA was performed, stratified by sex and adjusted for age and ancestry principal components. Mendelian randomisation (MR) and cluster analyses were used to examine causal effect of mJSW on HOA. FINDINGS: 50,745 individuals were included in the meta-analysis. 42 SNPs, which mapped to 39 loci, were identified. Mendelian randomisation (MR) revealed little evidence of a causal effect of mJSW on HOA (ORIVW 0.98 [95% CI 0.82-1.18]). However, MR-Clust analysis suggested the null MR estimates reflected the net effect of two distinct causal mechanisms cancelling each other out, one of which was protective, whereas the other increased HOA susceptibility. For the latter mechanism, all loci were positively associated with height, suggesting mechanisms leading to greater height and mJSW increase the risk of HOA in later life. INTERPRETATIONS: One group of mJSW loci reduce HOA risk via increased mJSW, suggesting possible utility as targets for chondroprotective therapies. The second group of mJSW loci increased HOA risk, despite increasing mJSW, but were also positively related to height, suggesting they contribute to HOA risk via a growth-related mechanism. FUNDING: Primarily funded by the Medical Research Council and Wellcome Trust.

Determining a Worldwide Prevalence of Oculocutaneous Albinism: A Systematic Review.

Purpose: The aim of this systematic review was to investigate the available data on the epidemiology of oculocutaneous albinism (OCA) around the world, and to determine whether a generalizable, worldwide prevalence figure could be proposed. Methods: Extensive literature search strategies were conducted, interrogating PubMed, Scopus, and Web of Science, to locate relevant literature. Ultimately 34 studies reporting original data were included for analysis. Results: Findings showed that most data were outdated, and only 6 of 34 articles (18%) were published after 2010. There were few good studies with sound methodology and large, clearly defined population samples. Only a small proportion of countries worldwide (26/193 [13%]) have produced prevalence figures for OCA. By continent, African studies were disproportionately represented (15/34 [44%]). The highest prevalence rates (range, 1 in 22 to 1 in 1300; mean, 1 in 464) were reported in population isolates. The mean prevalence from four African countries was 1 in 4264 (range, 1 in 1755 to 1 in 7900). Prevalence for three countries in Europe (mean, 1 in 12,000; range, 1 in 10,000 to 1 in 15,000) may be underestimated, as the phenotype, in fair-skinned populations, may be missed or misdiagnosed as ocular albinism or isolated visual impairment. Population rates may vary depending on local cultural factors (e.g., consanguineous matings) and may change over time. Conclusions: The prevalence of OCA varies widely between continents and population groups, and it is often influenced by local factors. It was not possible, therefore, to determine a single, generalizable worldwide prevalence rate for OCA, although continental rates for Africa and Europe are useful.