ABSTRACT
Mosaic chromosomal alteration (mCA) is referred to as large-scale somatic mutations on chromosomes, which results in diverse karyotypes in body. The mCA is regarded as one of the phenotypes of aging. Studies have revealed its associations with many chronic diseases such as hematopoietic cancers and cardiovascular diseases, but its genetic basis (e.g. genetic susceptibility variants) is still under-investigated. This paper reviews GWAS studies for mCA on autosomal chromosomes and sex chromosomes [mosaic loss of the Y chromosome (mLOY) and mosaic loss of the X chromosome (mLOX)] based on large population, respectively. Most of the genetic susceptibility loci found in studies for autosomal mCA were associated with copy-neutral loss of heterozygosity. The study of sex chromosome mCA focused on mosaic loss mutations. The number of genetic susceptibility loci for mLOY was high (up to 156), but it was relatively less for mLOX.
Subject(s)
Humans , Male , Genome-Wide Association Study/methods , Mosaicism , Genetic Predisposition to Disease , Chromosomes, Human, Y , MutationABSTRACT
Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.