A mendelian randomization study based on data from multiple cohorts conducted by Karani Santhanakrishnan Vimaleswaran and colleagues re-examines the causal nature of the relationship between vitamin D levels and obesity.

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24% P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.

Objective Systemic lupus erythematosus (SLE) and lupus nephritis (LN) disproportionately affect racial/ethnic minorities and lower socioeconomic status (SES) individuals. We investigated the epidemiology and sociodemographics of SLE and LN in the low-income U.S. Medicaid population. Methods We utilized Medicaid Analytic eXtract data, with billing claims from 47 states and Washington, D.C. for 23.9 million individuals, aged 18–65 years, enrolled in Medicaid for >3 months, 2000–2004. Individuals with SLE (> 3 visits, ICD-9 code 710.0, >30 days apart) and with LN (>2 ICD-9 codes for glomerulonephritis, proteinuria or renal failure) were identified. We calculated SLE and LN prevalence and incidence, stratified by sociodemographic categories, and adjusted for number of American College of Rheumatology (ACR) member rheumatologists and SES using a validated composite of U.S. Census variables. Results We identified 34,339 individuals with SLE (prevalence = 143.7/100,000) and 7,388 (21.5%) with LN (prevalence = 30.9/100,000). SLE prevalence was 6 times higher among women, nearly double in African American compared to White women, and highest in the U.S. South. LN prevalence was higher among all racial/ethnic groups compared to Whites. The lowest SES areas had the highest prevalence; areas with the fewest ACR rheumatologists had the lowest. SLE incidence was 23.2/100,000 person-years, and LN incidence was 6.9/100,000 person-years, with similar sociodemographic trends. Conclusions In this nationwide Medicaid population, there was sociodemographic variation in SLE and LN prevalence and incidence. Understanding the increased burden of SLE and its complications in this low-income population has implications for resource allocation and access to subspecialty care.