title: Combined genotype and haplotype tests for region-based association studies.
abstract: BACKGROUND
  Although single-SNP analysis has proven to be useful in identifying many disease-associated loci, region-based analysis has several advantages. Empirically, it has been shown that region-based genotype and haplotype approaches may possess much higher power than single-SNP statistical tests. Both high quality haplotypes and genotypes may be available for analysis given the development of next generation sequencing technologies and haplotype assembly algorithms.
  
  
  RESULTS
  As generally it is unknown whether genotypes or haplotypes are more relevant for identifying an association, we propose to use both of them with the purpose of preserving high power under both genotype and haplotype disease scenarios. We suggest two approaches for a combined association test and investigate the performance of these two approaches based on a theoretical model, population genetics simulations and analysis of a real data set.
  
  
  CONCLUSIONS
  Based on a theoretical model, population genetics simulations and analysis of a central corneal thickness (CCT) Genome Wide Association Study (GWAS) data set we have shown that combined genotype and haplotype approach has a high potential utility for applications in association studies.
authors: Human Genetics, Genome Institute of Singapore, Singapore, Singapore. zakharovs99@gis.a-star.edu.sg.
authors: Sergii
authors: S
authors: Zakharov
authors: Tien Yin
authors: TY
authors: Wong
authors: Tin
authors: T
authors: Aung
authors: Eranga Nishanthie
authors: EN
authors: Vithana
authors: Chiea Chuen
authors: CC
authors: Khor
authors: Agus
authors: A
authors: Salim
authors: Anbupalam
authors: A
authors: Thalamuthu
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study / Q000379:methods*; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide
references: Am J Hum Genet. 2011 Mar 11;88(3):273-82
references: 21353195
references: Genet Epidemiol. 2013 Jan;37(1):110-21
references: 23032573
references: Br J Dermatol. 2010 Aug;163(2):364-70
references: 20346027
references: Bioinformatics. 2008 Aug 15;24(16):i153-9
references: 18689818
references: Hum Mutat. 2012 Mar;33(3):521-9
references: 22190428
references: Genet Epidemiol. 2010 Sep;34(6):633-41
references: 20718046
references: Am J Hum Genet. 2011 Jul 15;89(1):82-93
references: 21737059
references: Am J Hum Genet. 2010 Jun 11;86(6):929-42
references: 20560208
references: Hum Mol Genet. 2011 Feb 15;20(4):649-58
references: 21098505
references: Genet Epidemiol. 2010 Feb;34(2):171-87
references: 19847924
references: BMC Proc. 2011 Nov 29;5 Suppl 9:S89
references: 22373048
references: Biol Psychiatry. 2011 Sep 15;70(6):528-36
references: 21683344
references: Am J Hum Genet. 2010 Jun 11;86(6):832-8
references: 20471002
references: Am J Hum Genet. 2007 Nov;81(5):1084-97
references: 17924348
references: Am J Ophthalmol. 2009 Apr;147(4):709-716.e1
references: 19152872
references: Ann Neurol. 2011 Dec;70(6):881-6
references: 22190362
references: Nat Genet. 2009 Mar;41(3):283-5
references: 19198611
references: Am J Hum Genet. 2001 Apr;68(4):978-89
references: 11254454
references: Am J Med Genet B Neuropsychiatr Genet. 2011 Jun;156B(4):490-2
references: 21445958
references: Hum Hered. 2008;65(3):121-8
references: 17934315
references: PLoS Genet. 2011 Feb 03;7(2):e1001289
references: 21304886
references: Nat Rev Genet. 2010 Nov;11(11):773-85
references: 20940738
references: Genet Epidemiol. 2007 Jul;31(5):383-95
references: 17410554
references: PLoS Genet. 2008 May 30;4(5):e1000083
references: 18516229
references: Ann Hum Genet. 2006 Jan;70(Pt 1):116-30
references: 16441261
references: PLoS Genet. 2009 Jun;5(6):e1000529
references: 19543373
references: PLoS Genet. 2009 Oct;5(10):e1000695
references: 19851460
references: Genet Epidemiol. 2008 Jan;32(1):1-8
references: 17630650
references: Genome Res. 2008 Aug;18(8):1336-46
references: 18676820
references: PLoS Genet. 2009 Feb;5(2):e1000384
references: 19214210
references: PLoS One. 2009;4(2):e4653
references: 19247474
references: J Rheumatol. 2010 May;37(5):987-92
references: 20231204
references: Hum Hered. 2002;53(2):79-91
references: 12037407
references: Genome Res. 2010 Sep;20(9):1165-73
references: 20508146
references: Graefes Arch Clin Exp Ophthalmol. 2008 Apr;246(4):587-92
references: 18196258
references: Mol Psychiatry. 2013 Apr;18(4):461-70
references: 22430674
references: Am J Hum Genet. 2010 Nov 12;87(5):728-35
references: 21055717
references: PLoS Genet. 2011 Mar;7(3):e1001322
references: 21408211
references: Eur J Hum Genet. 2001 Apr;9(4):291-300
references: 11313774
references: Ann Hum Genet. 2005 Nov;69(Pt 6):715-32
references: 16266410
references: BMC Bioinformatics. 2011 Jan 12;12:17
references: 21226955
references: Ophthalmic Epidemiol. 2009 Nov-Dec;16(6):325-36
references: 19995197
references: PLoS Genet. 2010 Nov 11;6(11):e1001202
references: 21085648
references: Hum Mol Genet. 2012 Jan 15;21(2):437-45
references: 21984434
references: Ophthalmic Epidemiol. 2007 Jan-Feb;14(1):25-35
references: 17365815
references: BMC Proc. 2011 Nov 29;5 Suppl 9:S23
references: 22373246
references: Nat Genet. 2006 Aug;38(8):904-9
references: 16862161
references: Arch Ophthalmol. 2008 Aug;126(8):1091-9
references: 18695104
references: Genet Epidemiol. 2009 May;33(4):308-16
references: 19025789