Long Runs of Homozygosity Are Correlated with Marriage Preferences across Global Population Samples.
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ABSTRACT:
SUBMITTER: Sahoo SA
PROVIDER: S-EPMC10497073 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Long Runs of Homozygosity Are Correlated with Marriage Preferences across Global Population Samples.
Sahoo Samali Anova SA Zaidi Rslan A RA Anagol Santosh S Mathieson Iain I
Human biology 20210101 3
Children of consanguineous unions carry long runs of homozygosity (ROH) in their genomes, due to their parents' recent shared ancestry. This increases the burden of recessive disease in populations with high levels of consanguinity and has been heavily studied in some groups. However, there has been little investigation of the broader effect of consanguinity on patterns of genetic variation on a global scale. This study, which collected published genetic data and information about marriage pract ...[more]
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| S-EPMC9490902 | biostudies-literature
Project description:ObjectivesHeight 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 methodsHere, we calculate the fraction of the genome composed of long runs of homozygosity (FROH) in a sample of 245 adults and use mixed effects models to assess its effect on height.ResultsWe find that Himba adults exhibit increased homozygosity. However, in contrast to previous studies in other populations, we do not find a significant effect of FROH 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 hg2=0.59 (SE ± 0.146), comparable to estimates reported in Europeans.DiscussionOur 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.
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Project description:BackgroundGenome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) influencing the risk of thyroid cancer (TC). Most cancer predisposition genes identified through GWASs function in a co-dominant manner, and studies have not found evidence for recessively functioning disease loci in TC. Our study examines whether homozygosity is associated with an increased risk of TC and searches for novel recessively acting disease loci.MethodsData from a previously conducted GWAS were used for the estimation of the proportion of phenotypic variance explained by all common SNPs, the detection of runs of homozygosity (ROH) and the determination of inbreeding to unravel their influence on TC.ResultsInbreeding coefficients were significantly higher among cases than controls. Association on a SNP-by-SNP basis was controlled by using the false discovery rate at a level of q* < 0.05, with 34 SNPs representing true differences in homozygosity between cases and controls. The average size, the number and total length of ROHs per person were significantly higher in cases than in controls. A total of 16 recurrent ROHs of rather short length were identified although their association with TC risk was not significant at a genome-wide level. Several recurrent ROHs harbor genes associated with risk of TC. All of the ROHs showed significant evidence for natural selection (iHS, Fst, Fay and Wu's H).ConclusionsOur results support the existence of recessive alleles in TC susceptibility. Although regions of homozygosity were rather small, it might be possible that variants within these ROHs affect TC risk and may function in a recessive manner.
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