ArticleAmerican journal of human genetics2006
Contrasting linkage-disequilibrium patterns between cases and controls as a novel association-mapping method.
Article in American journal of human genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Inter- and intra-chromosomal modulators of the APOE ɛ2 and ɛ4 effects on the Alzheimer's disease risk.GeroScience · 2023Article
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- Definitive roles of TOMM40-APOE-APOC1 variants in the Alzheimer's risk.Neurobiology of aging · 2022Article
- APOE region molecular signatures of Alzheimer's disease across races/ethnicities.Neurobiology of aging · 2020Article
- Genetic and regulatory architecture of Alzheimer's disease in theAlzheimer's & dementia (Amsterdam, Netherlands) · 2020Article
- Haplotype architecture of the Alzheimer's risk in theAlzheimer's & dementia (Amsterdam, Netherlands) · 2020Article
- Two-phase SSU and SKAT in genetic association studies.Journal of genetics · 2020Article
- Region-based interaction detection in genome-wide case-control studies.BMC medical genomics · 2019Article
- Apolipoprotein E region molecular signatures of Alzheimer's disease.Aging cell · 2018Article
- A UNIFIED FRAMEWORK FOR VARIANCE COMPONENT ESTIMATION WITH SUMMARY STATISTICS IN GENOME-WIDE ASSOCIATION STUDIES.The annals of applied statistics · 2017Article
- The Decay of Disease Association with Declining Linkage Disequilibrium: A Fine Mapping Theorem.Frontiers in genetics · 2016Article
- Reflections on the Field of Human Genetics: A Call for Increased Disease Genetics Theory.Frontiers in genetics · 2016Article
- A multi-SNP association test for complex diseases incorporating an optimal P-value threshold algorithm in nuclear families.BMC genomics · 2015Article
- Genetic association between germline JAK2 polymorphisms and myeloproliferative neoplasms in Hong Kong Chinese population: a case-control study.BMC genetics · 2014Article
- A fast multilocus test with adaptive SNP selection for large-scale genetic-association studies.European journal of human genetics : EJHG · 2014Article
- Accurate prediction of a minimal region around a genetic association signal that contains the causal variant.European journal of human genetics : EJHG · 2014Article
- A set-based association test identifies sex-specific gene sets associated with type 2 diabetes.Frontiers in genetics · 2014Article
- Evaluation of seven common lipid associated loci in a large Indian sib pair study.Lipids in health and disease · 2012Article
- Multivariate detection of gene-gene interactions.Genetic epidemiology · 2012Article
- Power of single- vs. multi-marker tests of association.Genetic epidemiology · 2012Article
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3 authors.
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Abstract
Identification and description of genetic variation underlying disease susceptibility, efficacy, and adverse reactions to drugs remains a difficult problem. One of the important steps in the analysis of variation in a candidate region is the characterization of linkage disequilibrium (LD). In a region of genetic association, the extent of LD varies between the case and the control groups. Separate plots of pairwise standardized measures of LD (e.g., D') for cases and controls are often presented for a candidate region, to graphically convey case-control differences in LD. However, the observed graphic differences lack statistical support. Therefore, we suggest the "LD contrast" test to compare whole matrices of disequilibrium between two samples. A common technique of assessing LD when the haplotype phase is unobserved is the expectation-maximization algorithm, with the likelihood incorporating the assumption of Hardy-Weinberg equilibrium (HWE). This approach presents a potential problem in that, in the region of genetic association, the HWE assumption may not hold when samples are selected on the basis of phenotypes. Here, we present a computationally feasible approach that does not assume HWE, along with graphic displays and a statistical comparison of pairwise matrices of LD between case and control samples. LD-contrast tests provide a useful addition to existing tools of finding and characterizing genetic associations. Although haplotype association tests are expected to provide superior power when susceptibilities are primarily determined by haplotypes, the LD-contrast tests demonstrate substantially higher power under certain haplotype-driven disease models.
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