Dataset Information

Integrative analysis of multiple case-control studies.

ABSTRACT: It is often challenging to share detailed individual-level data among studies due to various informatics and privacy constraints. However, it is relatively easy to pool together aggregated summary level data, such as the ones required for standard meta-analyses. Focusing on data generated from case-control studies, we present a flexible inference procedure that integrates individual-level data collected from an "internal" study with summary data borrowed from "external" studies. This procedure is built on a retrospective empirical likelihood framework to account for the sampling bias in case-control studies. It can incorporate summary statistics extracted from various working models adopted by multiple independent or overlapping external studies. It also allows for external studies to be conducted in a population that is different from the internal study population. We show both theoretically and numerically its efficiency advantage over several competing alternatives.

SUBMITTER: Zhang H

PROVIDER: S-EPMC8565848 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Integrative analysis of multiple case-control studies.

Zhang Han H Deng Lu L Wheeler William W Qin Jing J Yu Kai K

Biometrics 20210419 3

It is often challenging to share detailed individual-level data among studies due to various informatics and privacy constraints. However, it is relatively easy to pool together aggregated summary level data, such as the ones required for standard meta-analyses. Focusing on data generated from case-control studies, we present a flexible inference procedure that integrates individual-level data collected from an "internal" study with summary data borrowed from "external" studies. This procedure i ...[more]

PMID: 33768525

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Project description:BackgroundThe objective of the present study is to comprehensively evaluate the impact of the rs1800975 A/G polymorphism within the human xeroderma pigmentosum group A (XPA) gene on susceptibility to overall cancer by performing an integrative analysis of the current evidence.MethodsWe retrieved possible relevant publications from a total of six electronic databases (updated to April 2020) and selected eligible case-control studies for pooled assessment. P-values of association and odds ratio (OR) were calculated for the assessment of association effect. We also performed Begg's test and Egger's test, sensitivity analysis, false-positive report probability (FPRP) analysis, trial sequential analysis (TSA), and expression/splicing quantitative trait loci (eQTL/sQTL) analyses.ResultsIn total, 71 case-control studies with 19,257 cases and 30,208 controls from 52 publications were included for pooling analysis. We observed an enhanced overall cancer susceptibility in cancer cases compared with negative controls in the Caucasian subgroup analysis for the genetic models of allelic G vs. A, carrier G vs. A, homozygotic GG vs AA, heterozygotic AG vs. AA, dominant AG + GG vs. AA and recessive GG vs. AA + AG (P < 0.05, OR > 1). A similar positive conclusion was also detected in the "skin cancer" or "skin basal cell carcinoma (BCC)" subgroup analysis of the Caucasian population. Our FPRP analysis and TSA results further confirmed the robustness of the conclusion. However, our eQTL/sQTL data did not support the strong links of rs1800975 with the gene expression or splicing changes of XPA in the skin tissue. In addition, even though we observed a decreased risk of lung cancer under the homozygotic, heterozygotic and dominant models (P < 0.05, OR < 1) and an enhanced risk of colorectal cancer under the allelic, homozygotic, heterozygotic, dominant (P < 0.05, OR > 1), our data from FPRP analysis and another pooling analysis with only the population-based controls in the Caucasian population did not support the strong links between the XPA rs1800975 A/G polymorphism and the risk of lung or colorectal cancer.ConclusionsOur findings provide evidence of the close relationship between the XPA rs1800975 A/G polymorphism and susceptibility to skin cancer in the Caucasian population. The potential effect of XPA rs1800975 on the risk of developing lung or colorectal cancer still merits the enrollment of larger well-scaled studies.

Dataset Information

Integrative analysis of multiple case-control studies.

Publications

Integrative analysis of multiple case-control studies.

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