NDLI: Integration of Mouse and Human Genome-Wide Association Data Identifies KCNIP4 as an Asthma Gene

Content Provider	PubMed Central
Author	Himes, Blanca E. Sheppard, Keith Berndt, Annerose Leme, Adriana S. Myers, Rachel A. Gignoux, Christopher R. Levin, Albert M. Gauderman, W. James Yang, James J. Mathias, Rasika A. Isabelle, Romieu Torgerson, Dara G. Roth, Lindsey A. Huntsman, Scott Eng, Celeste Barbara, Klanderman John, Ziniti Jody, Senter-sylvia Szefler, Stanley J. Lemanske, Robert F. Zeiger, Robert S. Strunk, Robert C. Martinez, Fernando D. Boushey, Homer Chinchilli, Vernon M. Israel, Elliot Mauger, David Koppelman, Gerard H. Postma, Dirkje S. Nieuwenhuis, Maartje A. E. Vonk, Judith M. Lima, John J. Irvin, Charles G. Peters, Stephen P. Kubo, Michiaki Tamari, Mayumi Nakamura, Yusuke Litonjua, Augusto A. Tantisira, Kelan G. Raby, Benjamin A. Bleecker, Eugene R. Meyers, Deborah A. London, Stephanie J. Barnes, Kathleen C. Gilliland, Frank D. Williams, L. Keoki Burchard, Esteban G. Nicolae, Dan L. Ober, Carole Demeo, Dawn L. Silverman, Edwin K. Beverly, Paigen Churchill, Gary Shapiro, Steve D. Weiss, Scott T.
Editor	Zhang, Huiping
Copyright Year	2013
Abstract	Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR). The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify asthma-related genes by integrating AHR associations in mouse with human genome-wide association study (GWAS) data. We used Efficient Mixed Model Association (EMMA) analysis to conduct a GWAS of baseline AHR measures from males and females of 31 mouse strains. Genes near or containing SNPs with EMMA p-values <0.001 were selected for further study in human GWAS. The results of the previously reported EVE consortium asthma GWAS meta-analysis consisting of 12,958 diverse North American subjects from 9 study centers were used to select a subset of homologous genes with evidence of association with asthma in humans. Following validation attempts in three human asthma GWAS (i.e., Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG) and two human AHR GWAS (i.e., SHARP, DAG), the Kv channel interacting protein 4 (KCNIP4) gene was identified as nominally associated with both asthma and AHR at a gene- and SNP-level. In EVE, the smallest KCNIP4 association was at rs6833065 (P-value 2.9e-04), while the strongest associations for Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG were 1.5e-03, 1.0e-03, 3.1e-03 at rs7664617, rs4697177, rs4696975, respectively. At a SNP level, the strongest association across all asthma GWAS was at rs4697177 (P-value 1.1e-04). The smallest P-values for association with AHR were 2.3e-03 at rs11947661 in SHARP and 2.1e-03 at rs402802 in DAG. Functional studies are required to validate the potential involvement of KCNIP4 in modulating asthma susceptibility and/or AHR. Our results suggest that a useful approach to identify genes associated with human asthma is to leverage mouse AHR association data.
Related Links	http://dx.doi.org/10.1371/journal.pone.0056179
Starting Page	56179
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	2
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-02-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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

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