Power analysis for genome-wide association studies

Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
BMC Genetics (Impact Factor: 2.36). 02/2007; 8:58. DOI: 10.1186/1471-2156-8-58
Source: PubMed

ABSTRACT Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required.
The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs.
Genome-wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations.

  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper investigates various strategies for the management of solution space diversity within the context of a meta-hyper heuristic algorithm. The adaptive local search meta-hyper heuristic (ALSHH), which adaptively applies a local search algorithm when the population diversity strays outside a predetermined solution space diversity profile, is proposed. ALSHH was shown to compare favourably with algorithms making use of local search and diversity maintenance strategies applied at constant intervals throughout the optimization run. Good performance is also demonstrated with respect to two other popular multi-method algorithms.
    2013 BRICS Congress on Computational Intelligence & 11th Brazilian Congress on Computational Intelligence (BRICS-CCI & CBIC); 09/2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Population neuroscience endeavours to identify environmental and genetic factors that shape the function and structure of the human brain; it uses tools and knowledge of genetics, epidemiology, and cognitive neuroscience. Here, I focus on the application of population neuroscience in studies of brain development. By describing in some detail four existing large‐scale magnetic resonance (MR) imaging studies of typically developing children and adolescents, I provide an overview of their design, including population sampling and recruitment, assessments of environmental and genetic “exposures,” and measurements of brain and behavior “outcomes.” I then discuss challenges faced by investigators carrying out such MR‐based studies, including quality assurance, quality control and intersite coordination, and provide a brief overview of the achievements made so far. I conclude by outlining future directions vis‐à‐vis population neuroscience, such as design strategies that can be used to evaluate the presence of absence of causality in associations discovered by observational studies. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
    Human Brain Mapping 06/2010; 31(6). DOI:10.1002/hbm.21069 · 6.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of high-density single nucleotide polymorphisms (SNP) panels enables to interrogate genotypes for a large number of polymorphic sites simultaneously. Large-scale genotyping of a substantial number of individuals provides comprehensive insights into the genetic variability between as well as within populations. Genome-wide association studies based on genome-wide SNP panels offer a new powerful approach to identify genomic regions underlying phenotypic variation (QTL) of complex traits. Complex traits are determined by a limited number of loci explaining a large fraction of the genetic variation and a large number of of loci with infinitesimal effects. The present study identified two, four and twelve QTL regions for paternal calving ease, the development of supernumerary teats and for eye-are pigmentation in the highly structured German Fleckvieh population. In chapter 2 the mapping of two QTL for calving traits on Bos taurus autosome (BTA) 14 and 21 (P = 5.72 x 10-15 and P = 2.27 x 10-8, respectively) is reported after careful correction for population stratification. Calving traits are complex as they are influenced by sire-effects through the size of the calf as well as by dam-effects consisting mainly of the pelvic dimensions. The mapping was facilitated by applying breeding values for paternal calving ease to compensate the low heritability of calving traits. A genome-wide association study was performed using a principal components based approach to account for population stratification. Genotypes of 43,863 SNPs were available for 1800 bulls of the German Fleckvieh population. The two identified QTL affect both fetal and postnatal growth parameters. The two loci explain at least 10% of the genetic variation of calving difficulties in the Fleckvieh population. In chapter 3, the mapping of QTL predisposing to supernumerary teats based on progeny-derived phenotypes for udder clearness is reported. A principal components based and a mixed model based approach to account for population stratification were compared using real-world data. The study population consisted of 2467 bulls genotyped for 43,698 SNPs. Four QTL on BTA5, BTA6, BTA11 and BTA17 were identified. The four QTL explain a substantial fraction of the genetic variation of supernumerary teats. However, a large fraction of the genetic variation results from chromosomes without identified QTL. The findings confirm the proposed polygenic inheritance pattern of supernumerary teats in cattle. The four QTL pinpoint genes of the highly conserved Wnt-signalling pathway as the major genetic determinants for teat malformations in cattle. Chapter 4 reports a genome-wide association study for a special aspect of skin pigmentation in cattle. The study population consisted of 3579 bulls of the FV breed with a total of 320,186 progeny with phenotypes for ACOP. The proportion of daughters with ambilateral circumocular pigmentation was applied as phenotype with high heritability (h2 = 0.79). Genotypes were available for 658,385 SNPs. Twelve genomic regions were highly significantly associated. The identified QTL point to MCM6, PAX3, ERBB3, KITLG, LEF1, DKK2, KIT, CRIM1, ATRN, GSDMC, MITF and NBEAL2 as underlying genes for eye area pigmentation in cattle. The twelve QTL regions explain 56.91% of the heritability, while the entire SNP map accounts for 93.22% of the heritability. The results support a polygenic inheritance pattern of eye-area pigmentation in cattle and provide the basis for efficient genomic selection of animals that are less susceptible to serious eye diseases.
    01/2013, Degree: Dr. rer. nat., Supervisor: Ruedi Fries

Preview (2 Sources)

Available from