title: Imputation-based genomic coverage assessments of current human genotyping arrays.
abstract: Microarray single-nucleotide polymorphism genotyping, combined with imputation of untyped variants, has been widely adopted as an efficient means to interrogate variation across the human genome. "Genomic coverage" is the total proportion of genomic variation captured by an array, either by direct observation or through an indirect means such as linkage disequilibrium or imputation. We have performed imputation-based genomic coverage assessments of eight current genotyping arrays that assay from ~0.3 to ~5 million variants. Coverage was determined separately in each of the four continental ancestry groups in the 1000 Genomes Project phase 1 release. We used the subset of 1000 Genomes variants present on each array to impute the remaining variants and assessed coverage based on correlation between imputed and observed allelic dosages. More than 75% of common variants (minor allele frequency > 0.05) are covered by all arrays in all groups except for African ancestry, and up to ~90% in all ancestries for the highest density arrays. In contrast, less than 40% of less common variants (0.01 < minor allele frequency < 0.05) are covered by low density arrays in all ancestries and 50-80% in high density arrays, depending on ancestry. We also calculated genome-wide power to detect variant-trait association in a case-control design, across varying sample sizes, effect sizes, and minor allele frequency ranges, and compare these array-based power estimates with a hypothetical array that would type all variants in 1000 Genomes. These imputation-based genomic coverage and power analyses are intended as a practical guide to researchers planning genetic studies.
authors: Department of Biostatistics, University of Washington, Seattle, Washington, 98195.
authors: Sarah C
authors: SC
authors: Nelson
authors: Kimberly F
authors: KF
authors: Doheny
authors: Elizabeth W
authors: EW
authors: Pugh
authors: Jane M
authors: JM
authors: Romm
authors: Hua
authors: H
authors: Ling
authors: Cecelia A
authors: CA
authors: Laurie
authors: Sharon R
authors: SR
authors: Browning
authors: Bruce S
authors: BS
authors: Weir
authors: Cathy C
authors: CC
authors: Laurie
mesh_terms: D005787:Gene Frequency; D015894:Genome, Human; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012680:Sensitivity and Specificity
keywords: SNP microarrays; genome-wide association study; genomic coverage; power
references: Nat Genet. 2012 Jul 22;44(8):955-9
references: 22820512
references: Genet Epidemiol. 2008 Jul;32(5):387-95
references: 18271056
references: Am J Hum Genet. 2001 Jul;69(1):1-14
references: 11410837
references: Genomics. 2011 Dec;98(6):422-30
references: 21903159
references: Nat Rev Genet. 2010 Jul;11(7):499-511
references: 20517342
references: Nature. 2007 Oct 18;449(7164):851-61
references: 17943122
references: Nat Methods. 2013 Jan;10(1):5-6
references: 23269371
references: PLoS One. 2010 Mar 15;5(3):e9697
references: 20300623
references: Am J Hum Genet. 2012 Jan 13;90(1):7-24
references: 22243964
references: G3 (Bethesda). 2011 Nov;1(6):457-70
references: 22384356
references: Am J Hum Genet. 2008 Sep;83(3):311-21
references: 18691683
references: Nat Rev Genet. 2011 Sep 16;12(10):703-14
references: 21921926
references: Nature. 2012 Nov 1;491(7422):56-65
references: 23128226
references: Nat Rev Genet. 2013 Jun;14(6):379-89
references: 23657481
references: Genet Epidemiol. 2013 May;37(4):383-92
references: 23529720
references: Genomics. 2011 Aug;98(2):79-89
references: 21565264
references: N Engl J Med. 2010 Jul 8;363(2):166-76
references: 20647212
references: Mol Biol Evol. 2011 Aug;28(8):2231-7
references: 21368315
references: Genome Res. 2008 Aug;18(8):1354-61
references: 18493019
references: Nat Genet. 2006 Jun;38(6):659-62
references: 16715099
references: Am J Hum Genet. 2004 Jan;74(1):106-20
references: 14681826
references: Science. 2012 Jul 6;337(6090):64-9
references: 22604720
references: Hum Hered. 2011;72(3):153-60
references: 22004945
references: Am J Hum Genet. 2006 May;78(5):884-888
references: 16642443