統合化推進プログラムにおけるヒトゲノムバリエーションデータベース○ 澤井 裕美1 小池 麻子２ 豊田裕美1 山崎茉莉亜1 井ノ上 逸朗3 辻 省次４ 徳永 勝士1
1東京大学大学院医学系研究科, 2日立製作所

1 Human Genome Variation Databasein Japanese Integrated Database Project

研究開発グループ, 3遺伝研, 4東京大学医学部附属病院

5 Snapshots of GWAS (case-control) DB

Purposes：
1) Achieves continuous and intensive managements of humangenome variation/GWAS data by constructing database fordetected variation results/GWAS experimental results andanalysis results
2 Systematizes variations related to disease/virus tolerance ,drug response mainly in Asian/Japanese populations
3) Shares human genome variation /GWAS data among
researchers to promote genetics study

Retrieval by disease name, study id,
and SNP ID
Study comparison

Data filtering
View from disease list

Distribution of P-value overwhole genome

If you add“http://gwas.lifesciencedb.jp/cgi-bin/das” to the other DAS
server, you can see these
GWAS data from the DAS
server.

Cosmic data

Narcolepsy data view from Ensemble
Allelic test
Genotypic test,
Additive model,
Recessive model,
thesepermutation
Multiple testingcorrection

https://gwas.lifesciencedb.jp/

Individual genome

Reference genomes are addableRDF download is available

6 Snapshots of CNV association DB

Retrieval by SNP
and gene nameMutations’ genomic positions,
SNP’s kinds、a.a. mutation info,
case-control P-values, odds-ratios,
exp methods, clinical info., etc

CNV region of cases and controls
Low P-value regions
NBDC Datasharing committee（Public or sharedepending on datacategory）

CNV region

P-values

Repository data
CouncilAnalyses uponrequestData usage
application

Data usage
permission

Internal Database

GWAS-DB(GWAS, CNV, healthySNP)

Public Database
MaskeddataNGSvariation DB
Variation DB(Other experiments andliterature info.)
GWAS-DB(GWAS, CNV, healthySNP)Gene names

External
database

・Purposes
Overview of relationships between HLA haplotype and diseasesusceptibility, immunological response, and drug hypersensitivity
・Contents
Variations of each HLA haplotype
Relationships between HLA haplotype and diseases

7 Snapshots of Human genome variation DB

Cross search between diseases/variations/clinical info

Variation DB(Other experimentsand literature info.)

Cross search between diseases/variations/clinical infoNGSvariation DB

Data usage bysimple application

8 Snapshots of HLA DB

・Variations
mutations, smalls/long insertions/deletions, CNVs, repeatvariations

2 SNP’s quality control•Quality control of SNPs -Call rates, H-W equilibrium test statistics•Quality control of samples –Call rates, Heterozygosity•Quality control of population –PCA with HAPMAP data, qq-plot, etc.

・ Contents
・Healthy/disease related variations, experimental conditions,analysis method, reliability of variations
・Variations extracted by experimental results (exome 21samples (disease related)+68(healthy), HLA 1 sample)
・Variations manually extracted from literatures (35,000records)
・ Consensus sequence generations based on 1000 genome data,submitted data, and other healthy data

Differences between HLA haplotype in a whole region

Differences at base level in each HLA haplotype

3 Construction of Control DB
Purposes： Shares healthy control data among GWAS researchers
to use case-control study
Contents of HAL haplotype and disease and disease susceptibility, immunological response, and drug
hypersensitivity

Contents：•0.3-1 million genotype frequencies of SNP, allele frequencies,
Hardy-Weinberg equilibrium test statistics, call rates etc.
•Linkage disequilibrium （D’, r2）、Haplotype frequencies•SNP annotations （functions、chromosome positions, synonymous/synonymous SNPs）
Genotype concordance across platforms
Illumina

Affy6.0

9 Human genome variation DB contents
Distribution of variations in reference
genomes based on 1000 genome PJ data

Affy

Current data：
Omni-2.5
AXIOM
Illumina•Affy500K about 450 samples,
10.9920.996
Omni-2.5•Affy6.0 about 600 samples,
Affy6.00.992
10.995•Omini2.5 about 500 samples
Affy
0.996
0.995
1
• Axiom about 500 samples
AXIOM(400 samples)•Frequency dataand analysis results are downloadable.
Imputations based on the other platform data are also available.

Gene name search
Disease name search
Region search

Upper:JPTLower:CEU

Licensed under a Creative Commons表示4.0国際 (c)2016 澤井裕美（東京大学）

・RDF
SNPs data was converted RDF by Ensemble formats
and archived into Virtuoso.
GWAS data was partially converted into RDF by the programprovided by DBCLS.

4 Contents of Case-control DB•0.3-1million SNPs’ genotype frequencies, allele frequencies,
HWE test statistics, call rate, etc.
•Statistical results, genotypic test, allelic test, additive risk
model, recessive model, dominant model P-value, OR, 95% CI,AIC, etc.
•Multiple testing correction’s results such as Bonferroni, FDR,etc.
•Statistical results of relationships between Haplotypes andphenotypes.
•SNP’s annotations （functions, chromosome positions,synonymous/non-synonymous SNPs etc.）
Currently, 13 studies’ case-control data are open to public.
(26 studies are stored in internal DB)•DB contents:
about 40,000entries + 1,800Entries (HLA haplotype)
68 diseases, 1,500 disease related genes

10 Variation/GWAS Data acceptance policy•For GWAS, raw data, genotype (personal information), frequency
data, calculation results, each of them can be acceptable.
Overview of the variation distribution of
all diseases accumulated in HVDB

Overview of the disease-related mutations onprotein-protein network

Mutations on the pathway
Map (drawing software isprovided by the courtesy ofProf. Suzuki in Tokyo Univ.)•If the submitted data are not analyzed, the data will be analyzed
and stored to the GWAS database by us under the ethical review
permission.
•For other experimental results including NGS, only analyzed dataare acceptable.
•Submitted data can be internally used within one year.
•Registration of Clinical information is individually consulted.
This Human genome variation/GWAS database is a repository
database. We appreciate your data submission through NBDC
data access committee.
gwas@lifesciencedb.jp