title: Evaluation of power of the Illumina HumanOmni5M-4v1 BeadChip to detect risk variants for human complex diseases.
abstract: Although emerging sequencing technologies can characterize all genetic variants, the cost is still high. Illumina released the HumanOmni5M-4v1 (Omni5) genotype array with ~4.3M assayed SNPs, a much denser array compared with other available arrays. The Omni5 balances both cost and array density. In this article, we illustrate the power of Omni5 to detect genetic associations. The Omni5 includes variants with a wide range of minor allele frequencies down to <1%. The theoretical power calculation examples indicate the increased power of the Omni5 array compared with other arrays with lower density when evaluating associations with some known loci, although there are exceptions. We further evaluate the genetic associations between known loci and several quantitative traits in the Framingham Heart Study: femoral neck bone mineral density, lumbar spine bone mineral density and hippocampal volume. Finally, we search genome wide for novel associations using the Omni5 genotypes. We compare our association results from Affymetrix 500K+MIPS 50K arrays and two imputed data sets: (1) HapMap Phase II and (2) 1000 Genomes reference panel. We observed increased evidence for genotype-phenotype associations with smaller P-values for selected known loci using the Omni5 genotypes. With limited sample sizes, we identify novel variants with genome-wide significant P-values. Our observations support the notion that dense genotyping using the Omni5 can be powerful in detecting novel associated variants. Comparison with imputed data with higher density also suggests that imputation helps but cannot replace genotyping, especially when imputation quality is low.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Chuanhua
authors.initials: C
authors.lastname: Xing
authors.affiliation: Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Hebrew SeniorLife, Institute for Aging Research, Boston, MA, USA.|Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.|Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.|Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA, USA.
authors.forename: Anita L
authors.initials: AL
authors.lastname: DeStefano
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Heard-Costa
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: Hebrew SeniorLife, Institute for Aging Research, Boston, MA, USA.|Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Kiel
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.|Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA, USA.
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.|Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA, USA.
authors.forename: Josée
authors.initials: J
authors.lastname: Dupuis
mesh_terms: D015519:Bone Density / Q000235:genetics; D005820:Genetic Testing / Q000379:methods* / Q000592:standards; D055106:Genome-Wide Association Study / Q000379:methods* / Q000592:standards; D060005:Genotyping Techniques / Q000379:methods / Q000592:standards*; D006624:Hippocampus / Q000254:growth & development; D006801:Humans; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards; D009929:Organ Size / Q000235:genetics; D040641:Quantitative Trait Loci; D012680:Sensitivity and Specificity