A positively selected FBN1 missense variant reduces height in Peruvian individuals.

On average, Peruvian individuals are among the shortest in the world1. Here we show that Native American ancestry is associated with reduced height in an ethnically diverse group of Peruvian individuals, and identify a population-specific, missense variant in the FBN1 gene (E1297G) that is significantly associated with lower height. Each copy of the minor allele (frequency of 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). To our knowledge, this is the largest effect size known for a common height-associated variant. FBN1 encodes the extracellular matrix protein fibrillin 1, which is a major structural component of microfibrils. We observed less densely packed fibrillin-1-rich microfibrils with irregular edges in the skin of individuals who were homozygous for G1297 compared with individuals who were homozygous for E1297. Moreover, we show that the E1297G locus is under positive selection in non-African populations, and that the E1297 variant shows subtle evidence of positive selection specifically within the Peruvian population. This variant is also significantly more frequent in coastal Peruvian populations than in populations from the Andes or the Amazon, which suggests that short stature might be the result of adaptation to factors that are associated with the coastal environment in Peru.

Prevalence and incidence of epilepsy in Latin America and the Caribbean: A systematic review and meta-analysis of population-based studies.

OBJECTIVE: This study was undertaken to perform an updated systematic review and meta-analysis to estimate the pooled prevalence and incidence of epilepsy in Latin America and the Caribbean (LAC), describing trends over time, and exploring potential clinical and epidemiological factors explaining the heterogeneity in the region. METHODS: Observational studies assessing the incidence or prevalence of epilepsy in LAC countries up to March 2020 were systematically reviewed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Meta-analyses and cumulative analyses were performed using random-effects models. We assessed between-study heterogeneity with sensitivity, subgroup, and meta-regression analyses. Moreover, the quality of the included studies and the certainty of evidence were evaluated using the GRADE (grading of recommendation, assessment, development, and evaluation) approach. RESULTS: Overall, 40 studies (from 42 records) were included, 37 for prevalence analyses and six for incidence (312 387 inhabitants; 410 178 person-years). The lifetime prevalence was 14.09 per 1000 inhabitants (95% confidence interval [CI] = 11.72-16.67), for active epilepsy prevalence was 9.06 per 1000 individuals (95% CI = 6.94-11.44), and the incidence rate was 1.11 per 1000 person-years (95% CI = .65-1.70). These high estimates have been constant in the region since 1990. However, substantial statistical heterogeneity between studies and publication bias were found. The overall certainty of evidence was low. Methodological aspects (sample size) and countries' epidemiological characteristics such as access to sanitation services and child and adult mortality rates explained the high heterogeneity. Finally, the prevalence of epilepsy associated with neurocysticercosis (NCC) in the general population was high, and the proportion of NCC diagnosis among people living with epilepsy was 17.37%. SIGNIFICANCE: The epilepsy prevalence and incidence in LAC are higher than worldwide estimates, being constant since 1990 and strongly influenced by NCC. We identified high between-study heterogeneity and significant methodological limitations (e.g., heterogeneous definitions, lack of longitudinal studies). The region needs upgraded research using standardized definitions and diagnostic methods, and urgent action against preventable causes.