Heterozygosity Ratio, a Robust Global Genomic Measure of Autozygosity and Its Association with Height and Disease Risk.
AUTHORS
- NIHMSID: 0374636
ABSTRACT
Greater genetic variability in an individual is protective against recessive disease. However, existing quantifications of autozygosity, such as runs of homozygosity (ROH), have proven highly sensitive to genotyping density and have yielded inconclusive results about the relationship of diversity and disease risk. Using genotyping data from three datasets with over 43,000 subjects, we demonstrated that an alternative approach to quantifying genetic variability, the heterozygosity ratio, is a robust measure of diversity and is positively associated with the non-disease trait height and several disease phenotypes in subjects of European ancestry. The heterozygosity ratio is the number of heterozygous sites in an individual divided by the number of non-reference homozygous sites, and is strongly affected by the degree of genetic admixture of the population and varies across human populations. Unlike quantifications of ROH, the heterozygosity ratio is not sensitive to the density of genotyping performed. Our results establish the heterozygosity ratio as a powerful new statistic for exploring the patterns and phenotypic effects of different levels of genetic variation in populations.
Greater genetic variability in an individual is protective against recessive disease. However, existing quantifications of autozygosity, such as runs of homozygosity (ROH), have proven highly sensitive to genotyping density and have yielded inconclusive results about the relationship of diversity and disease risk. Using genotyping data from three datasets with over 43,000 subjects, we demonstrated that an alternative approach to quantifying genetic variability, the heterozygosity ratio, is a robust measure of diversity and is positively associated with the non-disease trait height and several disease phenotypes in subjects of European ancestry. The heterozygosity ratio is the number of heterozygous sites in an individual divided by the number of non-reference homozygous sites, and is strongly affected by the degree of genetic admixture of the population and varies across human populations. Unlike quantifications of ROH, the heterozygosity ratio is not sensitive to the density of genotyping performed. Our results establish the heterozygosity ratio as a powerful new statistic for exploring the patterns and phenotypic effects of different levels of genetic variation in populations.
Tags: Faculty Publications 2016