title: Using gene expression to improve the power of genome-wide association analysis.
abstract: OBJECTIVE
  Genome-wide association (GWA) studies have reported susceptible regions in the human genome for many common diseases and traits; however, these loci only explain a minority of trait heritability. To boost the power of a GWA study, substantial research endeavors have been focused on integrating other available genomic information in the analysis. Advances in high through-put technologies have generated a wealth of genomic data and made combining SNP and gene expression data become feasible.
  
  
  RESULTS
  In this paper, we propose a novel procedure to incorporate gene expression information into GWA analysis. This procedure utilizes weights constructed by gene expression measurements to adjust p values from a GWA analysis. RESULTS from simulation analyses indicate that the proposed procedures may achieve substantial power gains, while controlling family-wise type I error rates at the nominal level. To demonstrate the implementation of our proposed approach, we apply the weight adjustment procedure to a GWA study on serum interferon-regulated chemokine levels in systemic lupus erythematosus patients. The study results can provide valuable insights for the functional interpretation of GWA signals.
  
  
  BACKGROUND
  The R source code for implementing the proposed weighting procedure is available at http://www.biostat.umn.edu/∼yho/research.html.
authors.affiliation: Division of Biostatistics, University of Minnesota, Minneapolis, Minn., USA.
authors.forename: Yen-Yi
authors.initials: YY
authors.lastname: Ho
authors.forename: Emily C
authors.initials: EC
authors.lastname: Baechler
authors.forename: Ward
authors.initials: W
authors.lastname: Ortmann
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
authors.forename: Robert R
authors.initials: RR
authors.lastname: Graham
authors.forename: Tushar R
authors.initials: TR
authors.lastname: Bhangale
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
mesh_terms: D015415:Biomarkers / Q000097:blood; D054415:Chemokine CCL19 / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood; D003198:Computer Simulation; D005260:Female; D015870:Gene Expression; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D015415:Biomarkers; C515460:CCL19 protein, human; C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054357:Chemokine CXCL10
references.citation: Genet Epidemiol. 2007 Nov;31(7):741-7
references.pmid: 17549760
references.citation: Cell Mol Life Sci. 2011 May;68(9):1491-502
references.pmid: 21387144
references.citation: Biometrics. 2006 Mar;62(1):19-27
references.pmid: 16542225
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1631-6
references.pmid: 22307622
references.citation: Front Genet. 2013 May 31;4:103
references.pmid: 23755072
references.citation: PLoS Genet. 2012;8(11):e1003029
references.pmid: 23209423
references.citation: J Exp Med. 2003 Mar 17;197(6):711-23
references.pmid: 12642603
references.citation: Nature. 2008 Mar 27;452(7186):423-8
references.pmid: 18344981
references.citation: J Biol Chem. 2004 Dec 10;279(50):51729-38
references.pmid: 15383541
references.citation: J Biol Chem. 2007 Apr 27;282(17):13059-72
references.pmid: 17329253
references.citation: Bioinformatics. 2013 Apr 15;29(8):1026-34
references.pmid: 23419377
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2610-5
references.pmid: 12604793
references.citation: Clin Exp Immunol. 1979 Apr;36(1):145-50
references.pmid: 380854
references.citation: J Biopharm Stat. 2010 Mar;20(2):373-400
references.pmid: 20309764
references.citation: J Biol Chem. 1996 May 31;271(22):12687-90
references.pmid: 8663110
references.citation: Nature. 2008 Mar 27;452(7186):429-35
references.pmid: 18344982
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7
references.pmid: 19474294
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):582-7
references.pmid: 22184247
references.citation: Rheum Dis Clin North Am. 2000 May;26(2):199-213, v
references.pmid: 10768209
references.citation: N Engl J Med. 2008 Feb 28;358(9):929-39
references.pmid: 18305268
references.citation: Immunology. 2005 Jun;115(2):179-88
references.pmid: 15885123
references.citation: Stat Sci. 2009 Nov;24(4):398-413
references.pmid: 20711421
references.citation: Nat Immunol. 2005 Dec;6(12):1245-52
references.pmid: 16286920
references.citation: Nat Genet. 2013 Jun;45(6):580-5
references.pmid: 23715323
references.citation: Am J Hum Genet. 2006 Feb;78(2):243-52
references.pmid: 16400608
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3339-44
references.pmid: 12626739
references.citation: Hum Mol Genet. 2012 May 1;21(9):2111-23
references.pmid: 22286170
references.citation: Genome Biol Evol. 2013;5(11):2217-30
references.pmid: 24201373
references.citation: Biometrics. 2012 Mar;68(1):1-11
references.pmid: 21838806
references.citation: Autoimmunity. 2003 Dec;36(8):481-90
references.pmid: 14984025
references.citation: Arthritis Rheum. 2009 Oct;60(10):3098-107
references.pmid: 19790071
references.citation: Genome Res. 2011 Jan;21(1):68-73
references.pmid: 21147911
references.citation: Nat Genet. 2005 Jul;37(7):710-7
references.pmid: 15965475
references.citation: Nature. 2009 Oct 8;461(7265):747-53
references.pmid: 19812666
references.citation: PLoS Biol. 2008 May 6;6(5):e107
references.pmid: 18462017
references.citation: PLoS Genet. 2010 Apr 01;6(4):e1000888
references.pmid: 20369019
references.citation: Autoimmun Rev. 2013 Apr;12(6):687-9
references.pmid: 23201919
references.citation: PLoS Med. 2006 Dec;3(12):e491
references.pmid: 17177599
references.citation: PLoS One. 2012;7(12):e52260
references.pmid: 23300628
references.citation: Curr Opin Immunol. 2012 Oct;24(5):530-7
references.pmid: 22889593