Assessment of SNP-SNP interactions by using square contingency table analysis

Karadağ, Özay; Altun, Gökçen; Aktaş, Serpil

doi:10.1590/0001-3765202020190465

Cited by 2 publications

(1 citation statement)

References 14 publications

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“…Many research suggest that "missing heritability" in AD remains extensive with an estimated 25% of phenotypic variance unexplained by known variants, which may be explained by epistasis [5][6][7]. A single nucleotide polymorphism (SNP) is defined as single nucleotide alteration in a DNA sequence among individuals [8,9]. As a major drawback, in common GWAS, the focus is usually on SNPs that have significant individual effects [10,11].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Epistasis Study of Cerebrospinal Fluid Hyperphosphorylated Tau in ADNI Cohort

Chen

Jin

Liu

et al. 2023

Genes

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Alzheimer’s disease (AD) is the main cause of dementia worldwide, and the genetic mechanism of which is not yet fully understood. Much evidence has accumulated over the past decade to suggest that after the first large-scale genome-wide association studies (GWAS) were conducted, the problem of “missing heritability” in AD is still a great challenge. Epistasis has been considered as one of the main causes of “missing heritability” in AD, which has been largely ignored in human genetics. The focus of current genome-wide epistasis studies is usually on single nucleotide polymorphisms (SNPs) that have significant individual effects, and the amount of heritability explained by which was very low. Moreover, AD is characterized by progressive cognitive decline and neuronal damage, and some studies have suggested that hyperphosphorylated tau (P-tau) mediates neuronal death by inducing necroptosis and inflammation in AD. Therefore, this study focused on identifying epistasis between two-marker interactions at marginal main effects across the whole genome using cerebrospinal fluid (CSF) P-tau as quantitative trait (QT). We sought to detect interactions between SNPs in a multi-GPU based linear regression method by using age, gender, and clinical diagnostic status (cds) as covariates. We then used the STRING online tool to perform the PPI network and identify two-marker epistasis at the level of gene–gene interaction. A total of 758 SNP pairs were found to be statistically significant. Particularly, between the marginal main effect SNP pairs, highly significant SNP–SNP interactions were identified, which explained a relatively high variance at the P-tau level. In addition, 331 AD-related genes were identified, 10 gene–gene interaction pairs were replicated in the PPI network. The identified gene-gene interactions and genes showed associations with AD in terms of neuroinflammation and neurodegeneration, neuronal cells activation and brain development, thereby leading to cognitive decline in AD, which is indirectly associated with the P-tau pathological feature of AD and in turn supports the results of this study. Thus, the results of our study might be beneficial for explaining part of the “missing heritability” of AD.

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Section: Introductionmentioning

confidence: 99%

Genome-Wide Epistasis Study of Cerebrospinal Fluid Hyperphosphorylated Tau in ADNI Cohort

Chen

Jin

Liu

et al. 2023

Genes

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Advances in Quasi-Symmetry for Square Contingency Tables

Tahata

2022

Symmetry

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Contingency tables highlight relationships between categorical variables. Typically, the symmetry or marginal homogeneity of a square contingency table is evaluated. The original symmetry model often does not accurately fit a dataset due to its restrictions. Caussinus proposed a quasi-symmetry model which served as a bridge between symmetry and marginal homogeneity in square contingency tables. This study significantly influenced methodological developments in the statistical analysis of categorical data. Herein recent advances in quasi-symmetry are reviewed with an emphasis on four topics related to the author’s results: (1) modeling based on the f-divergence, (2) the necessary and sufficient condition of symmetry, (3) partition of test statistics for symmetry, and (4) measure of the departure from symmetry. The asymmetry model based on f-divergence enables us to express various asymmetries. Additionally, these models are useful to derive the necessary and sufficient conditions of symmetry with desirable properties. This review may be useful to consider the statistical modeling and the measure of symmetry for contingency tables with the same classifications.

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Assessment of SNP-SNP interactions by using square contingency table analysis

Cited by 2 publications

References 14 publications

Genome-Wide Epistasis Study of Cerebrospinal Fluid Hyperphosphorylated Tau in ADNI Cohort

Genome-Wide Epistasis Study of Cerebrospinal Fluid Hyperphosphorylated Tau in ADNI Cohort

Advances in Quasi-Symmetry for Square Contingency Tables

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