BackgroundAccurate assessment of health disparities requires unbiased knowledge of genetic risks in different populations. Unfortunately, most genome-wide association studies use genotyping arrays and European samples. Here, we integrate whole genome sequence data from global populations, results from thousands of genome-wide association studies (GWAS), and extensive computer simulations to identify how genetic disease risks can be misestimated.ResultsIn contrast to null expectations, we find that risk allele frequencies at known disease loci are significantly different for African populations compared to other continents. Strikingly, ancestral risk alleles are found at 9.51% higher frequency in Africa, and derived risk alleles are found at 5.40% lower frequency in Africa. By simulating GWAS with different study populations, we find that non-African cohorts yield disease associations that have biased allele frequencies and that African cohorts yield disease associations that are relatively free of bias. We also find empirical evidence that genotyping arrays and SNP ascertainment bias contribute to continental differences in risk allele frequencies. Because of these causes, polygenic risk scores can be grossly misestimated for individuals of African descent. Importantly, continental differences in risk allele frequencies are only moderately reduced if GWAS use whole genome sequences and hundreds of thousands of cases and controls. Finally, comparisons between uncorrected and corrected genetic risk scores reveal the benefits of considering whether risk alleles are ancestral or derived.ConclusionsOur results imply that caution must be taken when extrapolating GWAS results from one population to predict disease risks in another population.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1561-7) contains supplementary material, which is available to authorized users.

We examined the use of nasally administered fentanyl for the relief of agitation or discomfort after placement of bilateral myringotomy tubes in 150 children ages 6 mo to 5 yr using a prospective, double-blinded design. Fentanyl 2 microg/kg was found to reduce the incidence of agitation in these patients.

This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report.

Amgen and Merck.Dr. Genevieve M. Boland has a sponsored research agreements with Takeda Oncology, Palleon Pharmaceuticals, InterVenn Biosciences, and Olink Proteomics; serves as a consultant for Merck, InterVenn Biosciences, and Ankyra Therapeutics; served as a speaker for Novartis; and served on a scientific advisory board and steering committee for Nektar Therapeutics.All remaining authors have declared no conflicts of interest.

We conclude that the lowest dose of dexamethasone (0.0625 mg/kg) was as effective as the highest dose of dexamethasone (1.0 mg/kg) for preventing PONV or reducing the incidence of other secondary outcomes following tonsillectomy or adenotonsillectomy. There is no justification for the use of high-dose dexamethasone for the prevention of PONV in this cohort of children.