ArticleAmerican journal of human genetics2004
A powerful strategy to account for multiple testing in the context of haplotype analysis.
Article in American journal of human genetics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
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- Differences in genetic variation in antigen-processing machinery components and association with cervical carcinoma risk in two Indonesian populations.Immunogenetics · 2015Article
- The power comparison of the haplotype-based collapsing tests and the variant-based collapsing tests for detecting rare variants in pedigrees.BMC genomics · 2014Article
- Kernel-machine testing coupled with a rank-truncation method for genetic pathway analysis.Genetic epidemiology · 2014Article
- The CF-modifying gene EHF promotes p.Phe508del-CFTR residual function by altering protein glycosylation and trafficking in epithelial cells.European journal of human genetics : EJHG · 2014Article
- Construction and analysis of single nucleotide polymorphism-single nucleotide polymorphism interaction networks.IET systems biology · 2013Article
- CLCA4 variants determine the manifestation of the cystic fibrosis basic defect in the intestine.European journal of human genetics : EJHG · 2013Article
- Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease.BMC research notes · 2012Article
- Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapy.Radiation oncology (London, England) · 2012Article
- A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis.European archives of psychiatry and clinical neuroscience · 2012Article
- Initial interrogation, confirmation and fine mapping of modifying genes: STAT3, IL1B and IFNGR1 determine cystic fibrosis disease manifestation.European journal of human genetics : EJHG · 2011Article
- An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion.BMC medical genetics · 2011Article
- Contribution of 6p24 to non-syndromic cleft lip and palate in a Malay population: association of variants in OFC1.Journal of dental research · 2011Article
- The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study.BMC medical genetics · 2011Article
- Meta-analysis of haplotype-association studies: comparison of methods and empirical evaluation of the literature.BMC genetics · 2011Article
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2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Haplotypes--that is, linear arrangements of alleles on the same chromosome that were inherited as a unit--are expected to carry important information in the context of association fine mapping of complex diseases. In consideration of a set of tightly linked markers, there is an enormous number of different marker combinations that can be analyzed. Therefore, a severe multiple-testing problem is introduced. One method to deal with this problem is Bonferroni correction by the number of combinations that are considered. Bonferroni correction is appropriate for independent tests but will result in a loss of power in the presence of linkage disequilibrium in the region. A second method is to perform simulations. It is unfortunate that most methods of haplotype analysis already require simulations to obtain an uncorrected P value for a specific marker combination. Thus, it seems that nested simulations are necessary to obtain P values that are corrected for multiple testing, which, apparently, limits the applicability of this approach because of computer running-time restrictions. Here, an algorithm is described that avoids such nested simulations. We check the validity of our approach under two disease models for haplotype analysis of family data. The true type I error rate of our algorithm corresponds to the nominal significance level. Furthermore, we observe a strong gain in power with our method to obtain the global P value, compared with the Bonferroni procedure to calculate the global P value. The method described here has been implemented in the latest update of our program FAMHAP.
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