Search

SummaryAfrican populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multigenerational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within the African continent, as well as how within-Africa variation can be informative for broader variant interpretation; many variants appearing rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity within Africa.

Background Reducing readmissions among frequent users of psychiatric inpatient care could result in substantial cost savings to under-resourced mental health systems. Studies from high-income countries indicate that formal peer support can be an effective intervention for the reduction of readmissions among frequent users. Although in recent years formal peer support programmes have been established in mental health services in a few low- and middle-income countries (LMICs), they have not been rigorously evaluated. Methods This protocol describes a quasi-experimental difference-in-differences study conducted as part of a broader evaluation of the Brain Gain II peer support programme based at Butabika National Referral Hospital in Kampala, Uganda. The primary objective is to investigate whether frequent users of psychiatric inpatient care who have access to a peer support worker (PSW+) experience a greater reduction in rehospitalisation rates and number of days spent in hospital compared to those who do not have access to a peer support worker (PSW-). Frequent users, defined as adults diagnosed with either a mental disorder or epilepsy who have had three or more inpatient stays at Butabika over the previous 24 months, are referred to Brain Gain II by hospital staff on five inpatient wards. Frequent users who normally reside in a district where peer support workers currently operate (Kampala, Jinja, Wakiso and Mukono) are eligible for formal peer support and enter the PSW+ group. Participants in the PSW+ group are expected to receive at least one inpatient visit by a trained peer support worker before hospital discharge and three to six additional visits after discharge. Frequent users from other districts enter the PSW- group and receive standard care. Participants’ admissions data are extracted from hospital records at point of referral and six months following referral. Discussion To the best of our knowledge, this will be the first quasi-experimental study of formal peer support in a LMIC and the first to assess change in readmissions, an outcome of particular relevance to policy-makers seeking cost-effective alternatives to institutionalised mental health care.

BackgroundGenetic studies of biomedical phenotypes in underrepresented populations identify disproportionate numbers of novel associations. However, current genomics infrastructure--including most genotyping arrays and sequenced reference panels--best serves populations of European descent. A critical step for facilitating genetic studies in underrepresented populations is to ensure that genetic technologies accurately capture variation in all populations. Here, we quantify the accuracy of low-coverage sequencing in diverse African populations.ResultsWe sequenced the whole genomes of 91 individuals to high-coverage (≥20X) from the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study, in which participants were recruited from Ethiopia, Kenya, South Africa, and Uganda. We empirically tested two data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole genome sequencing data. We show that low-coverage sequencing at a depth of ≥4X captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1X) performed comparable to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation, with 4X sequencing detecting 45% of singletons and 95% of common variants identified in high-coverage African whole genomes.ConclusionThese results indicate that low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, including those that capture variation most common in Europeans and Africans. Low-coverage sequencing effectively identifies novel variation (particularly in underrepresented populations), and presents opportunities to enhance variant discovery at a similar cost to traditional approaches.