title: Heterozygosity Ratio, a Robust Global Genomic Measure of Autozygosity and Its Association with Height and Disease Risk.
abstract: Greater genetic variability in an individual is protective against recessive disease. However, existing quantifications of autozygosity, such as runs of homozygosity (ROH), have proved highly sensitive to genotyping density and have yielded inconclusive results about the relationship of diversity and disease risk. Using genotyping data from three data sets with >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 nondisease 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 nonreference 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.
authors: Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics and.
authors: David C
authors: DC
authors: Samuels
authors: Department of Cancer Biology and.
authors: Jing
authors: J
authors: Wang
authors: Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232.
authors: Fei
authors: F
authors: Ye
authors: Vanderbilt Epidemiology Center, Vanderbilt School of Medicine, Nashville, Tennessee 37232.
authors: Jing
authors: J
authors: He
authors: Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics and.
authors: Rebecca T
authors: RT
authors: Levinson
authors: Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics and.
authors: Quanhu
authors: Q
authors: Sheng
authors: Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics and.
authors: Shilin
authors: S
authors: Zhao
authors: Vanderbilt Genetics Institute, Department of Biomedical Informatics, Vanderbilt University Medical School, Nashville, Tennessee 37232.
authors: John A
authors: JA
authors: Capra
authors: Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics and.
authors: Yu
authors: Y
authors: Shyr
authors: Vanderbilt Epidemiology Center, Vanderbilt School of Medicine, Nashville, Tennessee 37232.
authors: Wei
authors: W
authors: Zheng
authors: Department of Cancer Biology and yan.guo@vanderbilt.edu.
authors: Yan
authors: Y
authors: Guo
mesh_terms: D001827:Body Height / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006579:Heterozygote; D006801:Humans; D011110:Polymorphism, Genetic
keywords: PheWAS; height; heterozygosity ratio; runs of homozygosity