NDLI: Addressing population-specific multiple testing burdens in genetic association studies

Please wait, while we are loading the content...

Addressing population-specific multiple testing burdens in genetic association studies

Content Provider	PubMed Central
Author	Sobota, Rafal S. Shriner, Daniel Nuri, Kodaman Goodloe, Robert Zheng, Wei Gao, Yu-tang Edwards, Todd L. Amos, Christopher I. Williams, Scott M.
Abstract	The number of effectively independent tests performed in genome-wide association studies and the corresponding genome-wide significance level varies by population. Therefore, a common p-value threshold may be inappropriate. To assess this, we estimated the number of independent SNPs for all Phase 3 HapMap samples using the LD pruning function in PLINK. We also used an autocorrelation-based approach to verify the HapMap findings, and tested it on 1000 Genomes data to estimate the number of independent tests in whole genome sequences. The number of effectively independent tests performed in genome-wide association studies (GWAS) varies by population, making a universal p-value threshold inappropriate. We estimated the number of independent SNPs in Phase 3 HapMap samples by: (1) the LD pruning function in PLINK, and (2) an autocorrelation-based approach. Autocorrelation was also used to estimate the number of independent SNPs in whole genome sequences from 1000 Genomes. Both approaches yielded consistent estimates of numbers of independent SNPs, which were used to calculate new population-specific thresholds for genome-wide significance. African populations had the most stringent thresholds (1.49×10−7 for YRI at r2=0.3), East Asian populations the least (3.75×10−7 for JPT at r2=0.3). We also assessed how using population-specific significance thresholds compared to using a single multiple testing threshold at the conventional 5×10−8 cutoff. Applied to a previously published GWAS of melanoma in Caucasians, our approach identified two additional genes, both previously associated with the phenotype. In a Chinese breast cancer GWAS, our approach identified 48 additional genes, 19 of which were in or near genes previously associated with the phenotype. We conclude that the conventional genome-wide significance threshold generates an excess of Type 2 errors, particularly in GWAS performed on more recently founded populations.
Related Links	http://dx.doi.org/10.1111/ahg.12095
Starting Page	136
File Format	PDF
ISSN	14691809
e-ISSN	14691809
Journal	Annals of human genetics
Issue Number	2
Volume Number	79
Language	English
Publisher Date	2015-03-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

Central Library (ISO-9001:2015 Certified)
Indian Institute of Technology Kharagpur
Kharagpur, West Bengal, India | PIN - 721302

See location in the Map
03222 282435
Mail: support@ndl.gov.in

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