Comparison of statistical power between 2x2 allele frequency and allele positivity tables in case-control studies of complex disease genes

AbstractMatched case-control designs are currently used in many biomedical applications. To ensure high efficiency and statistical power in identifying features that best discriminate cases from controls, it is important to account for the use of matched designs. However, in the setting of high dimensional data, few variable selection methods account for matching. Bayesian approaches to variable selection have several advantages, including the fact that such approaches visit a wider range of model subsets. In this paper, we propose a variable selection method to account for case-control matching in a Bayesian context and apply it using simulation studies, a matched brain imaging study conducted at Massachusetts General Hospital, and a matched cardiovascular biomarker study conducted by the High Risk Plaque Initiative.

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Comparison of SNP Genotypes Related to Proliferative Vitreoretinopathy (PVR) across Slovenian and European Subpopulations

Journal of Ophthalmology ◽

10.1155/2018/8761625 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7

Author(s):

Xhevat Lumi ◽

Mateja M. Jelen ◽

Daša Jevšinek Skok ◽

Emanuela Boštjančič ◽

Metka Ravnik-Glavač ◽

...

Keyword(s):

Allele Frequency ◽

Association Studies ◽

Case Control ◽

Genotype Distribution ◽

Healthy Controls ◽

Case Control Studies ◽

Ensembl Database ◽

Functional Polymorphisms ◽

Genotype Frequencies ◽

Frequency Changes

The present study investigated the distribution of genotypes within single nucleotide polymorphisms (SNPs) in genes, related to PVR pathogenesis across European subpopulations. Genotype distributions of 42 SNPs among 96 Slovenian healthy controls were investigated and compared to genotype frequencies in 503 European individuals (Ensembl database) and their subpopulations. Furthermore, a case-control status was simulated to evaluate effects of allele frequency changes on statistically significant results in gene-association studies investigating functional polymorphisms. In addition, 96 healthy controls were investigated within 4 SNPs: rs17561 (IL1A), rs2069763 (IL2), rs2229094 (LTA), and rs1800629 (TNF) in comparison to PVR patients. Significant differences (P<0.05) in distribution of genotypes among 96 Slovenian participants and a European population were found in 10 SNPs: rs3024498 (IL10), rs315952 (IL1RN), rs2256965 (LST1), rs2256974 (LST1), rs909253 (LTA), rs2857602 (LTA), rs3138045 (NFKB1A), rs3138056 (NFKB1A), rs7656613 (PDGFRA), and rs1891467 (TGFB2), which additionally showed significant differences in genotype distribution among European subpopulations. This analysis also showed statistically significant differences in genotype distributions between healthy controls and PVR patients in rs17561 of the IL1A gene (OR, 3.00; 95% CI, 0.77–11.75; P=0.036) and in rs1800629 of the TNF gene (OR, 0.48; 95% CI, 0.27–0.87; P=0.014). Furthermore, we have shown that a small change (0.02) in minor allele frequency (MAF) significantly affects the statistical p value in case-control studies. In conclusion, the study showed differences in genotype distributions in healthy populations across different European countries. Differences in distribution of genotypes may have had influenced failed replication results in previous PVR-related SNP-association studies.

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Association between Transforming Growth Factor Alpha TaqI Polymorphism and Susceptibility to the Nonsyndromic Cleft Lip and/or Palate in an Iranian Population: A Case Control Study

World Journal of Peri & Neonatology ◽

10.18502/wjpn.v2i1.2806 ◽

2020 ◽

Author(s):

Abdolhamid Amooee ◽

Seyed Mohammadreza Niktabar ◽

Mohammad Javad Akbarian-Bafghi ◽

Majid Morovati-Sharifabad ◽

Mohamad Hosein Lookzadeh ◽

...

Keyword(s):

Allele Frequency ◽

Cleft Lip ◽

Case Control Study ◽

Transforming Growth Factor ◽

Case Control ◽

Iranian Population ◽

Case Control Studies ◽

Increased Risk ◽

Significant Difference ◽

Control Study

Background: The TGF-α TaqI C >T polymorphism is a well-characterized variant for nonsyndromic cleft lip and/or palate (NS CL/P), but it has shown inconsistent results of association with nonsyndromic CL/P across a number of studies. Thus, we have performed this case-control study to clarify the association between the TGF-α TaqI C >T polymorphism and NS CL/P risk. Methods: One-hundred ten cases with NSCL/P and 110 controls were recruited to the current study. We have genotyped the TGF-α TaqI C >T polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The odds ratio (OR) and 95% confidence interval (CI) were applied for strength of association TGF-α TaqI C >T polymorphism with NSCL/P. Results: The TGF-α TaqI C >T polymorphism CC, CT and TT genotypes frequencies in the NSCL/P cases were 30.9%, 57.3% and 11.8%, respectively while the corresponding frequencies in the controls were 37.3%, 52.7% and 10.0%, respectively. The frequency of C and T alleles in the case were 59.5% and 40.5%, respectively while the corresponding allelic frequencies in the controls were 63.6% and 36.4%. There was no significant difference in the genotype and allele frequency for TGF-α TaqI C >T polymorphism between cases and controls. The minor allele frequency (MAF) of TGF-α TaqI C >T polymorphism among healthy controls was 0.36. Conclusion: Our study indicates that the TGF-α TaqI C>T polymorphism was not significantly associated with increased risk of NS CL/P in the Iranian population. However, our results still need to be confirmed by further large and well-designed case-control studies.

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Simple F Test Reveals Gene-Gene Interactions in Case-Control Studies

Bioinformatics and Biology Insights ◽

10.4137/bbi.s9867 ◽

2012 ◽

Vol 6 ◽

pp. BBI.S9867 ◽

Cited By ~ 1

Author(s):

Guanjie Chen ◽

Ao Yuan ◽

Jie Zhou ◽

Amy R. Bentley ◽

Adebowale Adeyemo ◽

...

Keyword(s):

Complex Disease ◽

Association Studies ◽

Parametric Method ◽

Case Control ◽

Gene Interactions ◽

Ratio Test ◽

Genome Wide Association Studies ◽

Case Control Studies ◽

F Test ◽

Howard University

Missing heritability is still a challenge for Genome Wide Association Studies (GWAS). Gene-gene interactions may partially explain this residual genetic influence and contribute broadly to complex disease. To analyze the gene-gene interactions in case-control studies of complex disease, we propose a simple, non-parametric method that utilizes the F-statistic. This approach consists of three steps. First, we examine the joint distribution of a pair of SNPs in cases and controls separately. Second, an F-test is used to evaluate the ratio of dependence in cases to that of controls. Finally, results are adjusted for multiple tests. This method was used to evaluate gene-gene interactions that are associated with risk of Type 2 Diabetes among African Americans in the Howard University Family Study. We identified 18 gene-gene interactions ( P < 0.0001). Compared with the commonly-used logistical regression method, we demonstrate that the F-ratio test is an efficient approach to measuring gene-gene interactions, especially for studies with limited sample size.

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1304Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the EPIC study

International Journal of Epidemiology ◽

10.1093/ije/dyab168.685 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Marie Breeur ◽

Pietro Ferrari ◽

Julie Schmidt ◽

Ruth Travis ◽

Tim Key ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Risk ◽

Statistical Power ◽

Conditional Logistic Regression ◽

Total Sample ◽

Case Control ◽

Cancer Site ◽

Case Control Studies ◽

Cancer Types ◽

Pan Cancer

Abstract Background Metabolomics studies in cancer epidemiology have mostly focused on single metabolite-cancer site associations. Pan-cancer analyses may have larger statistical power when identifying metabolites showing consistent associations across cancer sites, while allowing the identification of site-specific associations. Methods Data from seven cancer-specific case-control studies nested within the European Prospective Investigation into Cancer and Nutrition Cohort (EPIC) were pooled, resulting in a total sample of 7,957 case-control pairs from eight cancer types (breast, colorectal, endometrial, gallbladder, kidney, localized prostate and advanced prostate cancer, and hepatocellular carcinoma). A total of 117 pre-diagnostic blood metabolites were measured. After clustering the most highly correlated ones together, we studied the association between 50 features (metabolites or clusters of metabolites) and cancer risk in multivariate penalized conditional logistic regression models controlled for body mass index using the data shared lasso. Results We identified: (i) 8 features with consistent associations across cancer sites: e.g., glutamine and C4-acylcarnitine, one cluster of lysophosphatidylcholines and one of phosphatidylcholines were inversely associated with cancer, while C10-acylcarnitine, valine and proline showed positive associations; (ii) 11 features with heterogeneous associations across cancer sites: e.g., arginine was positively associated with colorectal cancer only, while one cluster of sphingomyelins was associated inversely with hepatocellular carcinoma and positively with endometrial cancer. Conclusions Our pan-cancer analysis notably identified metabolites showing consistent associations with cancer risk across different cancer-types. Key messages Our results could lead to the identification of common pathways shared across different cancer types.

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Association of FcεRIβ polymorphisms with risk of asthma and allergic rhinitis: evidence based on 29 case–control studies

Bioscience Reports ◽

10.1042/bsr20180177 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 2

Author(s):

Huanhuan Guo ◽

Tao Peng ◽

Ping Luo ◽

Huabin Li ◽

Shuo Huang ◽

...

Keyword(s):

Risk Factors ◽

Statistical Power ◽

Meta Analysis ◽

Allergic Diseases ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Case Control Studies ◽

Potential Risk Factors ◽

Genetic And Environmental Factors ◽

The Stability

Purpose: Accumulating evidence has shown that allergic diseases are caused by a complex interaction of genetic and environmental factors, some single nucleotide polymorphisms (SNPs) existing in high-affinity IgE receptor β chain (FcεRIβ) are potential risk factors for allergic diseases. However, the results have been inconsistent and inconclusive due to the limited statistical power in individual study. Thus, we conducted a meta-analysis to systematically evaluate the association between FcεRIβ SNPs and allergic diseases risk. Methods: Eligible studies were collected from PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and WanFang databases. Pooled odd ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the relationships between five polymorphisms (E237G, -109 C/T, RsaI_in2, RsaI_ex7, and I181L) and the risk of allergic diseases by using five genetic models. In addition, the stability of our analysis was evaluated by publication bias, sensitivity, and heterogeneity analysis. Results: Overall, a total of 29 case–control studies were included in this meta-analysis. We found that E237G (B vs. A: OR = 1.28, 95% CI = 1.06–1.53, P<0.001, I2 = 63.1%) and -109 C/T (BB vs. AA + AB: OR = 1.58, 95%CI = 1.26–1.98, P<0.001, I2 = 66.4%) were risk factors for allergic diseases. Conclusion: Our meta-analysis suggests that polymorphisms in FcεRIβ may be associated with the development of allergic diseases.

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