Basic Science and Pathogenesis.

Background: With a rapidly aging population, South Korea anticipates a surge in Alzheimer disease (AD). However, the genetic basis of AD in Koreans is not well understood.

Method: We sequenced the genomes of 3,540 Koreans (1,583 AD cases and 1,957 controls) older than age 60 and performed a genome-wide association study (GWAS) of AD using logistic regression models that included covariates for age, sex, five ancestry principal components, and an empirical genetic relationship matrix.

Whole-genome sequencing study in Koreans identifies novel loci for Alzheimer's disease.

Introduction: The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood.

Methods: We performed an AD genome-wide association study using whole-genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single-nucleotide polymorphism array data from 2978 Japanese (1336 AD cases, 1642 controls). Significant findings were evaluated by pathway enrichment and differential gene expression analysis in brain tissue from controls and AD cases with and without dementia prior to death.

A comparative investigation of single nucleotide variant calling for a personal non-Caucasian sequencing sample.

Background: Dropping cost and increasing clinical application of whole genome sequencing (WGS) lead a necessity of efficient (accurate and rapid) variant calling procedures from a personal WGS data (n = 1). A number of variant calling pipelines have been introduced utilizing the human genome reference GRCh38 as a reference and a benchmark dataset called 'NA12878', which are both 'standard' but limited ethnic origin. Considering the nature of variant calling algorithms and recent updates in sequencing protocol, however, it is necessary to revisit the efficiency of the current best pipelines for a personal WGS data from diverse ethnicity.

A comparative investigation of variant calling and genotyping for a single non-Caucasian whole genome.

Most genome benchmark studies utilize hg38 as a reference genome (based on Caucasian and African samples) and 'NA12878' (a Caucasian sequencing read) for comparison. Here, we aimed to elucidate whether 1) ethnic match or mismatch between the reference genome and sequencing reads produces a distinct result; 2) there is an optimal work flow for single genome data. We assessed the performance of variant calling pipelines using hg38 and a Korean genome (reference genomes) and two whole-genome sequencing (WGS) reads from different ethnic origins: Caucasian (NA12878) and Korean.