NDLI: Stepwise approach to SNP-set analysis illustrated with the Metabochip and colorectal cancer in Japanese Americans of the Multiethnic Cohort

Content Provider	Springer Nature : BioMed Central
Author	Cologne, John Loo, Lenora Shvetsov, Yurii B. Misumi, Munechika Lin, Philip Haiman, Christopher A. Wilkens, Lynne R. Le Marchand, Loïc
Abstract	Background Common variants have explained less than the amount of heritability expected for complex diseases, which has led to interest in less-common variants and more powerful approaches to the analysis of whole-genome scans. Because of low frequency (low statistical power), less-common variants are best analyzed using SNP-set methods such as gene-set or pathway-based analyses. However, there is as yet no clear consensus regarding how to focus in on potential risk variants following set-based analyses. We used a stepwise, telescoping approach to analyze common- and rare-variant data from the Illumina Metabochip array to assess genomic association with colorectal cancer (CRC) in the Japanese sub-population of the Multiethnic Cohort (676 cases, 7180 controls). We started with pathway analysis of SNPs that are in genes and pathways having known mechanistic roles in colorectal cancer, then focused on genes within the pathways that evidenced association with CRC, and finally assessed individual SNPs within the genes that evidenced association. Pathway SNPs downloaded from the dbSNP database were cross-matched with Metabochip SNPs and analyzed using the logistic kernel machine regression approach (logistic SNP-set kernel-machine association test, or sequence kernel association test; SKAT) and related methods. Results The TGF-β and WNT pathways were associated with all CRC, and the WNT pathway was associated with colon cancer. Individual genes demonstrating the strongest associations were TGFBR2 in the TGF-β pathway and SMAD7 (which is involved in both the TGF-β and WNT pathways). As partial validation of our approach, a known CRC risk variant in SMAD7 (in both the TGF-β and WNT pathways: rs11874392) was associated with CRC risk in our data. We also detected two novel candidate CRC risk variants (rs13075948 and rs17025857) in TGFBR2, a gene known to be associated with CRC risk. Conclusions A stepwise, telescoping approach identified some potentially novel risk variants associated with colorectal cancer, so it may be a useful method for following up on results of set-based SNP analyses. Further work is required to assess the statistical characteristics of the approach, and additional applications should aid in better clarifying its utility.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-018-4910-8.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/s12864-018-4910-8
Journal	BMC Genomics
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2018-07-09
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Colorectal cancer Genome-wide association study Metabochip array Multiethnic Cohort SNP set analysis
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

A time-dependent genome-wide SNP-SNP interaction analysis of chicken body weight

High-density 80 K SNP array is a powerful tool for genotyping G. hirsutum accessions and genome analysis

Genome-wide CNV analysis replicates the association between GSTM1 deletion and bladder cancer: a support for using continuous measurement from SNP-array data

Genome wide association and genomic prediction for growth traits in juvenile farmed Atlantic salmon using a high density SNP array

Supervised categorical principal component analysis for genome-wide association analyses

Genome-wide association studies for immunoglobulin concentrations in colostrum and serum in Chinese Holstein

SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese

Genome wide association study reveals novel QTL for barley yellow dwarf virus resistance in wheat

Stepwise approach to SNP-set analysis illustrated with the Metabochip and colorectal cancer in Japanese Americans of the Multiethnic Cohort

Similar Documents

A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

A time-dependent genome-wide SNP-SNP interaction analysis of chicken body weight

High-density 80 K SNP array is a powerful tool for genotyping G. hirsutum accessions and genome analysis

Genome-wide CNV analysis replicates the association between GSTM1 deletion and bladder cancer: a support for using continuous measurement from SNP-array data

Genome wide association and genomic prediction for growth traits in juvenile farmed Atlantic salmon using a high density SNP array

Supervised categorical principal component analysis for genome-wide association analyses

Genome-wide association studies for immunoglobulin concentrations in colostrum and serum in Chinese Holstein

SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese

Genome wide association study reveals novel QTL for barley yellow dwarf virus resistance in wheat

Stepwise approach to SNP-set analysis illustrated with the Metabochip and colorectal cancer in Japanese Americans of the Multiethnic Cohort