R PheWAS: data analysis and plotting tools for phenome-wide association studies in the R environment

被引：266

作者：

Carroll, Robert J. ^{[1
]}

Bastarache, Lisa ^{[1
]}

Denny, Joshua C. ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA

[2] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA

来源：

BIOINFORMATICS | 2014年 / 30卷 / 16期

关键词：

GENOME;

D O I：

10.1093/bioinformatics/btu197

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Phenome-wide association studies (PheWAS) have been used to replicate known genetic associations and discover new phenotype associations for genetic variants. This PheWAS implementation allows users to translate ICD-9 codes to PheWAS case and control groups, perform analyses using these and/or other phenotypes with covariate adjustments and plot the results. We demonstrate the methods by replicating a PheWAS on rs3135388 (near HLA-DRB, associated with multiple sclerosis) and performing a novel PheWAS using an individual's maximum white blood cell count (WBC) as a continuous measure. Our results for rs3135388 replicate known associations with more significant results than the original study on the same dataset. Our PheWAS of WBC found expected results, including associations with infections, myeloproliferative diseases and associated conditions, such as anemia. These results demonstrate the performance of the improved classification scheme and the flexibility of PheWAS encapsulated in this package.

引用

页码：2375 / 2376

页数：2

共 8 条

[1] Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci [J].

De Jager, Philip L. ;

Jia, Xiaoming ;

Wang, Joanne ;

de Bakker, Paul I. W. ;

Ottoboni, Linda ;

Aggarwal, Neelum T. ;

Piccio, Laura ;

Raychaudhuri, Soumya ;

Tran, Dong ;

Aubin, Cristin ;

Briskin, Rebeccah ;

Romano, Susan ;

Baranzini, Sergio E. ;

McCauley, Jacob L. ;

Pericak-Vance, Margaret A. ;

Haines, Jonathan L. ;

Gibson, Rachel A. ;

Naeglin, Yvonne ;

Uitdehaag, Bernard ;

Matthews, Paul M. ;

Kappos, Ludwig ;

Polman, Chris ;

McArdle, Wendy L. ;

Strachan, David P. ;

Evans, Denis ;

Cross, Anne H. ;

Daly, Mark J. ;

Compston, Alastair ;

Sawcer, Stephen J. ;

Weiner, Howard L. ;

Hauser, Stephen L. ;

Hafler, David A. ;

Oksenberg, Jorge R. .

NATURE GENETICS, 2009, 41 (07) :776-U26

[2] Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data [J].

Denny, Joshua C. ;

Bastarache, Lisa ;

Ritchie, Marylyn D. ;

Carroll, Robert J. ;

Zink, Raquel ;

Mosley, Jonathan D. ;

Field, Julie R. ;

Pulley, Jill M. ;

Ramirez, Andrea H. ;

Bowton, Erica ;

Basford, Melissa A. ;

Carrell, David S. ;

Peissig, Peggy L. ;

Kho, Abel N. ;

Pacheco, Jennifer A. ;

Rasmussen, Luke V. ;

Crosslin, David R. ;

Crane, Paul K. ;

Pathak, Jyotishman ;

Bielinski, Suzette J. ;

Pendergrass, Sarah A. ;

Xu, Hua ;

Hindorff, Lucia A. ;

Li, Rongling ;

Manolio, Teri A. ;

Chute, Christopher G. ;

Chisholm, Rex L. ;

Larson, Eric B. ;

Jarvik, Gail P. ;

Brilliant, Murray H. ;

McCarty, Catherine A. ;

Kullo, Iftikhar J. ;

Haines, Jonathan L. ;

Crawford, Dana C. ;

Masys, Daniel R. ;

Roden, Dan M. .

NATURE BIOTECHNOLOGY, 2013, 31 (12) :1102-+

[3] Variants Near FOXE1 Are Associated with Hypothyroidism and Other Thyroid Conditions: Using Electronic Medical Records for Genome- and Phenome-wide Studies [J].

Denny, Joshua C. ;

Crawford, Dana C. ;

Ritchie, Marylyn D. ;

Bielinski, Suzette J. ;

Basford, Melissa A. ;

Bradford, Yuki ;

Chai, High Seng ;

Bastarache, Lisa ;

Zuvich, Rebecca ;

Peissig, Peggy ;

Carrell, David ;

Ramirez, Andrea H. ;

Pathak, Jyotishman ;

Wilke, Russell A. ;

Rasmussen, Luke ;

Wang, Xiaoming ;

Pacheco, Jennifer A. ;

Kho, Abel N. ;

Hayes, M. Geoffrey ;

Weston, Noah ;

Matsumoto, Martha ;

Kopp, Peter A. ;

Newton, Katherine M. ;

Jarvik, Gail P. ;

Li, Rongling ;

Manolio, Teri A. ;

Kullo, Iftikhar J. ;

Chute, Christopher G. ;

Chisholm, Rex L. ;

Larson, Eric B. ;

McCarty, Catherine A. ;

Masys, Daniel R. ;

Roden, Dan M. ;

de Andrade, Mariza .

AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 89 (04) :529-542

[4] PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations [J].

Denny, Joshua C. ;

Ritchie, Marylyn D. ;

Basford, Melissa A. ;

Pulley, Jill M. ;

Bastarache, Lisa ;

Brown-Gentry, Kristin ;

Wang, Deede ;

Masys, Dan R. ;

Roden, Dan M. ;

Crawford, Dana C. .

BIOINFORMATICS, 2010, 26 (09) :1205-1210

[5] A new multipoint method for genome-wide association studies by imputation of genotypes [J].

Marchini, Jonathan ;

Howie, Bryan ;

Myers, Simon ;

McVean, Gil ;

Donnelly, Peter .

NATURE GENETICS, 2007, 39 (07) :906-913

[6] Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network [J].

Pendergrass, Sarah A. ;

Brown-Gentry, Kristin ;

Dudek, Scott ;

Frase, Alex ;

Torstenson, Eric S. ;

Goodloe, Robert ;

Ambite, Jose Luis ;

Avery, Christy L. ;

Buyske, Steve ;

Buzkova, Petra ;

Deelman, Ewa ;

Fesinmeyer, Megan D. ;

Haiman, Christopher A. ;

Heiss, Gerardo ;

Hindorff, Lucia A. ;

Hsu, Chu-Nan ;

Jackson, Rebecca D. ;

Kooperberg, Charles ;

Le Marchand, Loic ;

Lin, Yi ;

Matise, Tara C. ;

Monroe, Kristine R. ;

Moreland, Larry ;

Park, Sungshim L. ;

Reiner, Alex ;

Wallace, Robert ;

Wilkens, Lynn R. ;

Crawford, Dana C. ;

Ritchie, Marylyn D. .

PLOS GENETICS, 2013, 9 (01)

[7] Visually integrating and exploring high throughput Phenome-Wide Association Study (PheWAS) results using PheWAS-View [J].

Pendergrass, Sarah A. ;

Dudek, Scott M. ;

Crawford, Dana C. ;

Ritchie, Marylyn D. .

BIODATA MINING, 2012, 5

[8] PLINK: A tool set for whole-genome association and population-based linkage analyses [J].

Purcell, Shaun ;

Neale, Benjamin ;

Todd-Brown, Kathe ;

Thomas, Lori ;

Ferreira, Manuel A. R. ;

Bender, David ;

Maller, Julian ;

Sklar, Pamela ;

de Bakker, Paul I. W. ;

Daly, Mark J. ;

Sham, Pak C. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (03) :559-575

← 1 →