A hidden Markov random field model for genome-wide association studies.
Genome-wide association studies (GWAS) are increasingly utilized for identifying novel susceptible genetic variants for complex traits, but there is little consensus on analysis methods for such data. Most commonly used methods include single single nucleotide polymorphism (SNP) analysis or haplotyp...
| Publicado en: | Biostatistics Vol. 11; no. 1; pp. 139 - 151 |
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| Autores principales: | , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Oxford University Press / USA
Jan2010
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105283261&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105283261 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14654644 N58 jtl: Biostatistics issn: 14654644 maglogo: N pubinfo: dt: Jan2010 vid: 11 iid: 1 pid: 622 pub: Oxford University Press / USA artinfo: ui: 105283261 NLM19822692 2010525686 10.1093/biostatistics/kxp043 NLM19822692 PMC2800164 105283261 ppf: 139 ppct: 12 formats: tig: atl: A hidden Markov random field model for genome-wide association studies. aug: au: Li H Wei Z Maris J Li, Hongzhe Wei, Zhi Maris, John affil: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA sug: subj: Sequence Analysis Methods Probability Models, Statistical Algorithms Chromosomes Computer Simulation Disease Genotype Human Genetics Neuroblastoma Polymorphism, Genetic ab: Genome-wide association studies (GWAS) are increasingly utilized for identifying novel susceptible genetic variants for complex traits, but there is little consensus on analysis methods for such data. Most commonly used methods include single single nucleotide polymorphism (SNP) analysis or haplotype analysis with Bonferroni correction for multiple comparisons. Since the SNPs in typical GWAS are often in linkage disequilibrium (LD), at least locally, Bonferroni correction of multiple comparisons often leads to conservative error control and therefore lower statistical power. In this paper, we propose a hidden Markov random field model (HMRF) for GWAS analysis based on a weighted LD graph built from the prior LD information among the SNPs and an efficient iterative conditional mode algorithm for estimating the model parameters. This model effectively utilizes the LD information in calculating the posterior probability that an SNP is associated with the disease. These posterior probabilities can then be used to define a false discovery controlling procedure in order to select the disease-associated SNPs. Simulation studies demonstrated the potential gain in power over single SNP analysis. The proposed method is especially effective in identifying SNPs with borderline significance at the single-marker level that nonetheless are in high LD with significant SNPs. In addition, by simultaneously considering the SNPs in LD, the proposed method can also help to reduce the number of false identifications of disease-associated SNPs. We demonstrate the application of the proposed HMRF model using data from a case-control GWAS of neuroblastoma and identify 1 new SNP that is potentially associated with neuroblastoma. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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