CAS Array: design and assessment of a genotyping array for Chinese biobanking

Abstract

Background Chronic diseases are becoming a critical challenge to the aging Chinese population. Biobanks with extensive genomic and environmental data offer opportunities to elucidate the complex gene-environment interactions underlying their aetiology. Genome-wide genotyping array remains an efficient approach for large-scale genomic data collection. However, most commercial arrays have reduced performance for biobanking in Chinese. Materials and Methods Deep whole-genome sequencing data from 2 641 Chinese individuals were used as a reference to develop the CAS array, a custom designed genotyping array for precision medicine. Evaluation of the array was performed by comparing data from 384 individuals assayed both by the array and whole-genome sequencing. Validation of its mitochondrial copy number estimating capacity was conducted by examining its association with established covariates among 10 162 Chinese elderly. Results The CAS Array adopts the proven Axiom technology and is restricted to a number of 652 429 single nucleotide polymorphism (SNP) markers. Its call rate of 99.79% and concordance rate of 99.89% are both higher than commercial arrays. Its imputation-based genome coverage reached 98.3% for common SNPs and 63.0% for low-frequency SNPs, both comparable to commercial arrays with larger SNP capacity. After validating its mitochondrial copy number estimates, we developed a publicly available software tool to facilitate the array utility. Conclusion Based on the recent advance in genomic science, we designed and implemented a high-throughput and low-cost genotyping array. It is more cost-effective than commercial arrays for large scale Chinese biobanking.

CYP2C19 Loss‐of‐Function Variants Associated With Long‐Term Ischemic Stroke Events During Clopidogrel Treatment in the Chinese Population

“…Genotyping of CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) was performed using the CAS Biobank Axiom Array, which was designed according to a high-quality Chinese genomic reference panel. 23 Based on the carriage of CYP2C19 *2 and *3 variants, patients with 2 or more *2 or *3 variants were classified as poor metabolizers (PMs), those with one *2 or *3 variant (*1/*2 or *1/*3) were defined as intermediate metabolizers (IMs), and those without any *2 or *3 variant were classified as normal metabolizers (NMs). Individuals carrying at least one *2 or *3 variant were defined as LoF variant carriers.…”

Association of mitochondrial DNA copy number with chronic kidney disease in older adults

“…Mitochondrial DNA copy number (mtDNA-CN) were estimated from the whole genome genotyping Array data. Detailed data processing has been described elsewhere [22]. Furthermore, we applied a linear regression model to control for the potential confounding effects of age, sex, white blood cell counts, platelet counts, blood collection date, and batch variability.…”