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

ABSTRACT: 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

SUBMITTER: Asgari S 

PROVIDER: S-EPMC7410362 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature