Aims: Identify disease-related genes and mobile element variations in Japanese/Development for Japanese population-specific reference panels

Methods: Genomic DNA samples were genotyped by following methods: Human610-Quad BeadChip, HumanHap550v3 Genotyping BeadChip, HumanOmniExpress-12 BeadChip, HumanExome BeadChip, OmniExpressExome BeadChip (Illumina), high-density oligonucleotide arrays (Perlegen Sciences), or Invader (Hologic Japan). Genome-Wide Association Studies (GWAS) for myocardial infarction (MI) , type II diabetes mellitus (T2DM), Atopic dermatitis (AD), atrial fibrillation (AF), Body Mass Index (BMI), primary open-angle glaucoma (POAG), 58 quantitative traits, age at menarche / menopause, smoking behaviour, height, 42 diseases (among them, the samples of 4 diseases were partially overlapped with those of previous release), dietary habits, and coronary artery disease were performed using about 500-2700K variants. Meta analyses for T2DM with diabetic nephropathy and for T2DM were also performed. SNP array analysis for 51 diseases registered in Biobank Japan were performed. Whole-genome sequencing analyses for 1,026 + 1,007 patients, who were registered Bio Bank Japan from 2003 - 2007, 1,765 myocardial infarction patients, 199 dementia patients, 256 + 2,067 gastric cancer patients, 617 colorectal cancer patients and 2,162 diabetes patients were performed with Illumina HiSeq 2500/X Five. Target sequencing analyses of 11 hereditary breast cancer genes in 7,104 breast cancer patients and 23,731 controls, 8 hereditary prostate cancer genes in 7,636 prostate cancer patients and 12,366 controls, 23 genes related to clonal hematopoiesis in 11,234 subjects extracted from approximately 200,000 subjects registered in Biobank Japan between fiscal years 2003 to 2007, 27 cancer-predisposing genes in 1,009 pancreatic cancer patients, 12,606 colorectal cancer patients, 740 renal cell cancer patients, 1,982 lymphoma patients, 10,366 gastric cancer patients and 23,780 + 5,996 + 37,592 controls and 13 renal cell carcinoma-related genes in 740 renal cell cancer patients and 5,996 controls were performed with Illumina HiSeq 2500. Also targeted sequencing was performed on the coding regions of TP53 in 140,597 individuals, including those with breast cancer, stomach cancer, colon cancer, heart failure, stroke, etc. SNP array analysis for 11,234 subjects was performed. A new reference panel was build with WGS data of the biobank Japan project (N=7,472 or 3,256) and the 1KGPp3v5 ALL (N=2,504). Sex-stratified genome-wide association studies using a Cox proportional hazard model under the assumption of the additive genetic model were performed. Associations of genetic variants estimated by saddle point estimation using SPACox software were also evaluated. A mobile element variation (MEV) search tool, MEGAnE, was applied to 4,880 WGS conducted in BBJ and 24,933 MEVs were found. Genome-wide association study for atrial fibrillation was performed in 9,826 cases and 140,446 controls. A subsequent cross-ancestry meta-analysis with European GWAS (60,620 cases and 970,216 controls; http://csg.sph.umich.edu/willer/public/afib2018) and Finnish GWAS (7,244 cases and 56,378 controls; FinnGenn; https://www.finngen.fi/en) was performed (77,690 cases and 1,167,040 controls in total). Polygenic risk score was constructed based on the cross-ancestry meta-analysis of atrial fibrillation.

Targets: Participants for the Tailor-made Medical Treatment Program (BioBank Japan: BBJ)