Examination of runs of homozygosity in relation to height in an endogamous Namibian population

Abstract

Objectives: Height is a complex, highly heritable polygenic trait subject to both genetic composition and environmental influences. Recent studies suggest that a large proportion of height heritability is determined by the cumulative effect of many low allele frequency variants across the genome. Previous research has also identified an inverse relationship between height and runs of homozygosity (ROH); however, this has yet to be examined within African populations. We aim to identify this association within the Himba, an endogamous Namibian population who are recently bottlenecked, resulting in elevated haplotype sharing and increased homozygosity.Materials and Methods: Here, we calculate the fraction of the genome composed of long runs of homozygosity (F ROH ) in a sample of 245 adults and use mixed effects models to assess its effect on height.Results: We find that Himba adults exhibit increased homozygosity. However, in contrast to previous studies in other populations, we do not find a significant effect of F ROH on height within the Himba. We further estimated heritability of height, noting both an enrichment of distant relatives and greater developmental homogeneity across households; we find that h 2 g ¼ 0:59 (SE ± 0.146), comparable to estimates reported in Europeans.Discussion: Our results may be due to other environmental variables we were not able to include, measurement error, or low statistical power, but may also imply that phenotypic expression resulting from increased homozygosity may vary from population to population.

Genotypic and phenotypic consequences of domestication in dogs

“…We observed that the relationship between height and F ROH is positive within all breed dogs (Figure 4). This positive effect size (β) opposes recently published work in human populations (Swinford et al 2023; Joshi et al 2015; McQuillan et al 2012). This may be a result of combining the β from multiple sizes of dogs (i.e.…”

Increased homozygosity due to endogamy results in fitness consequences in a human population

“…In an idealized outbred population, the F ROH expectation for the offspring of first cousins would be 0.0625, and F ROH calculated using a minimum threshold of 1,500 kb to call ROH is comparable to a pedigree estimate of inbreeding ( 14 ). The mean F ROH 1,500 of 2.6% observed in the Himba, and first reported in Swinford et al ( 37 ), is therefore between the values expected for the offspring of second cousins and offspring of first cousins in an outbred population ( 15 ). However, this measure is not applicable to a population like the Himba who have elevated levels of IBD sharing (see below).…”

“…We identified ROH and calculated FROH as in Swinford et al ( 37 ). To calculate F ROH , we first calculated the length of the genome tested in the SNP arrays by summing the lengths between the first and last SNPs genotyped on each chromosome.…”