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.

Highlights Coronovirus Disease 2019 (COVID-19) has serious implications for older adults. Qualitative analysis of an online discussion by older adults with frailty. We analyzed 60 posts using a general inductive analytic method. Themes included impacts on daily life, perceptions, information, and technology use. Our study provides insight into ways to support older adults in pandemics.

Prostate cancer incidence and mortality rates in African and African American men are greatly elevated compared with other ethnicities. This disparity is likely explained by a combination of social, environmental, and genetic factors. A large number of susceptibility loci have been reported by genome-wide association studies (GWAS), but the contribution of these loci to prostate cancer disparities is unclear. Here, we investigated the population structure of 68 previously reported GWAS loci and calculated genetic disparity contribution statistics to identify SNPs that contribute the most to differences in prostate cancer risk across populations. By integrating GWAS results with allele frequency data, we generated genetic risk scores for 45 African and 19 non-African populations. Tests of natural selection were used to assess why some SNPs have large allele frequency differences across populations. We report that genetic predictions of prostate cancer risks are highest for West African men and lowest for East Asian men. These differences may be explained by the out-of-Africa bottleneck and natural selection. A small number of loci appear to drive elevated prostate cancer risks in men of African descent, including rs9623117, rs6983267, rs10896449, rs10993994, and rs817826. Although most prostate cancer-associated loci are evolving neutrally, there are multiple instances where alleles have hitchhiked to high frequencies with linked adaptive alleles. For example, a protective allele at 2q37 appears to have risen to high frequency in Europe due to selection acting on pigmentation. Our results suggest that evolutionary history contributes to the high rates of prostate cancer in African and African American men. A small number of genetic variants cause an elevated risk of prostate cancer in men of West African descent. .

Background Compared to other types of dementia, family caregivers of people with Lewy body dementia (LBD) report higher stress levels and more severe depressive symptoms. Although several digital support interventions for caregivers of persons with dementia exist, few target LBD specifically or leverage a fully remote and asynchronous approach suitable for pandemic circumstances. Objective We performed a pilot evaluation of a digital intervention designed to help caregivers of people with LBD address challenges they have experienced, with the end goal of reducing psychological distress in this population. Methods We recruited 15 family caregivers of people with LBD to participate in the quasi-experimental, single-arm, mixed methods study titled Virtual Online Communities for Aging Life Experience–Lewy Body Dementia (VOCALE-LBD). The study offers an 8-week web-based intervention that uses a digital discussion platform and involves moderation, peer-to-peer support, didactic training, and problem-solving skill enactment. Results Participants’ baseline characteristics were the following: mean age 66 (SD 8) years; 14 of 15 (93%) of them were female; all (15/15, 100%) were White; and 8 (53%) of them had at least a postgraduate degree. Throughout the intervention, participants engaged in weekly web-based discussions, generating a total of 434 posts (average 4 posts per week). Attrition was 20% (3/15). Upon study exit, participants showed the following average improvements: 3.0 (SD 6.0) in depression, 8.3 (SD 16.7) in burden, 2.9 (SD 6.8) in stress, and 0.3 (SD 0.8) in loneliness. When looking at the proportion of participants with clinically significant improvement versus those with a worsening of ≥0.5 SD for each outcome, we observed net improvements of 50% (6/12), 33% (4/12), 25% (3/12), and 25% (3/12) in depression, loneliness, burden, and stress, respectively. In terms of the benefits of participation, participants reported that participation helped them “a great deal” to (1) improve their understanding of LBD (9/12, 75%), (2) gain confidence in dealing with difficult behaviors of the care recipient (6/12, 50%), and (3) improve in one’s abilities to provide care to the care recipient (4/12, 33%). Conclusions The study generated promising feasibility and preliminary efficacy data for a low-cost, web-based intervention designed for caregivers of persons with LBD. Though the study was not powered for significance, we observed nominal average and net improvements in important psychological outcomes. Moreover, many caregivers reported that study participation helped them better understand the disease, feel more confident in dealing with difficult behaviors of the care recipient, and improve their ability to care for the care recipient. If validated in future studies, the intervention could be an accessible, on-demand resource for caregivers, enabling them to engage in moderated remote discussions with peers at their own convenience in terms of location, time of the day, and frequency.

Background: There is a need for interventions to promote health management of older adults with pre-frailty and frailty. Technology poses promising solutions, but questions exist about effective delivery. Objectives: We present the results of a mixed-methods pilot evaluation of Virtual Online Communities for Older Adults (VOCALE), an 8-week intervention conducted in the northwestern United States, in which participants shared health-related experiences and applied problem solving skills in a Facebook group. Methods: We performed a mixed-methods process evaluation, integrating quantitative and qualitative data, to characterize the intervention and its effects. We focus on four areas: health-related measures (health literacy and self-efficacy), participation, problem solving skills enacted, and subjective feedback. Results: Eight older adults with pre-frailty and frailty (age = 82.7 ± 6.6 years) completed the study. There was an upward trend in health literacy and health self-efficacy post-intervention. Participants posted at least two times per week. Content analysis of 210 posts showed participants were able to apply the problem solving skills taught, and exit interviews showed participants’ increased awareness of the need to manage health, and enjoyment in learning about others. Conclusion: This mixed-methods evaluation provides insight into feasibility and design considerations for online interventions to promote health management among vulnerable older adults.