Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in the development of diseases. Many have collected data on large numbers of genetic markers but are not familiar with available methods to assess their association with complex diseases. Statistical methods have been developed for analyzing the relation between large numbers of genetic and environmental predictors to disease or disease-related variables in genetic association studies.In this commentary we discuss logistic regression analysis, neural networks, including the parameter decreasing method (PDM) and genetic programming optimized neural networks (GPNN) and several non-parametric methods, which include the set association approach, combinatorial partitioning method (CPM), restricted partitioning method (RPM), multifactor dimensionality reduction (MDR) method and the random forests approach. The relative strengths and weaknesses of these methods are highlighted.Logistic regression and neural networks can handle only a limited number of predictor variables, depending on the number of observations in the dataset. Therefore, they are less useful than the non-parametric methods to approach association studies with large numbers of predictor variables. GPNN on the other hand may be a useful approach to select and model important predictors, but its performance to select the important effects in the presence of large numbers of predictors needs to be examined. Both the set association approach and random forests approach are able to handle a large number of predictors and are useful in reducing these predictors to a subset of predictors with an important contribution to disease. The combinatorial methods give more insight in combination patterns for sets of genetic and/or environmental predictor variables that may be related to the outcome variable. As the non-parametric methods have different strengths and weaknesses we conclude that to approach genetic association studies using the case-control design, the application of a combination of several methods, including the set association approach, MDR and the random forests approach, will likely be a useful strategy to find the important genes and interaction patterns involved in complex diseases.
Scabies is a skin infestation with the mite Sarcoptes scabiei causing itch and rash and is a major risk factor for bacterial skin infections and severe complications. Here, we evaluated the treatment outcome of 2866 asylum seekers who received (preventive) scabies treatment before and during a scabies intervention programme (SIP) in the main reception centre in the Netherlands between January 2014 and March 2016. A SIP was introduced in the main national reception centre based on frequent observations of scabies and its complications amongst Eritrean and Ethiopian asylum seekers in the Netherlands. On arrival, all asylum seekers from Eritrea or Ethiopia were checked for clinical scabies signs and received ivermectin/permethrin either as prevention or treatment. A retrospective cohort study was conducted to compare the reinfestations and complications of scabies in asylum seekers who entered the Netherlands before and during the intervention and who received ivermectin/permethrin. In total, 2866 asylum seekers received treatment during the study period (January 2014 –March 2016) of which 1359 (47.4%) had clinical signs of scabies. During the programme, most of the asylum seekers with scabies were already diagnosed on arrival as part of the SIP screening (580 (64.7%) of the 897). Asylum seekers with more than one scabies episode reduced from 42.0% (194/462) before the programme to 27.2% (243/897) during the programme (RR = 0.64, 95% CI = 0.55–0.75). Development of scabies complications later in the asylum procedure reduced from 12.3% (57/462) to 4.6% (41/897). A scabies prevention and treatment programme at start of the asylum procedure was feasible and effective in the Netherlands; patients were diagnosed early and risk of reinfestations and complications reduced. To achieve a further decrease of scabies, implementation of the programme in multiple asylum centres may be needed.
Nonparametric approaches have been developed that are able to analyze large numbers of single nucleotide polymorphisms (SNPs) in modest sample sizes. These approaches have different selection features and may not provide similar results when applied to the same dataset. Therefore, we compared the results of three approaches (set association, random forests and multifactor dimensionality reduction [MDR]) to select from a total of 93 candidate SNPs a subset of SNPs that are important in determining high-density lipoprotein (HDL)-cholesterol levels. The study population consisted of a random sample from a Dutch monitoring project for cardiovascular disease risk factors and was dichotomized into cases (low HDL-cholesterol, n = 533) and non-cases (high HDL-cholesterol, n = 545) based on gender-specific median values for HDL cholesterol. Clearly, all three approaches prioritized three SNPs as important (CETP Taq1B, CETP-629 C/A and LPL Ser447X). Two SNPs with weaker main effects were additionally prioritized by random forests (APOC3 3175 G/C and CCR2 Val62Ile), whereas MTHFR 677 C/T was selected in combination with CETP Taq1B as best model by MDR. Obtained p-values for the selected models were significant for the set association approach (p =.0019), random forests (p<.01) and MDR (p<.02). In conclusion, the application of a combination of multi-locus methods is a useful approach in genetic association studies to select a well-defined set of important SNPs for further statistical and epidemiological interpretation, providing increased confidence and more information compared with the application of only one method.
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