PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 14614240

Group sequential study designs in genetic-epidemiological case-control studies.

Inke R König·Andreas Ziegler
View original source ↗Export metadata ↓

Abstract

OBJECTIVE: In past years, the focus of genetic-epidemiological studies has shifted to analyzing complex diseases. Here, single genes often contribute only little to the manifestation of traits so that many probands have to be included in a study to reliably detect small effects. To reduce the number of required phenotypings and genotypings and thus facilitate analyzing complex traits, sequential study designs can be applied. METHODS: For sequential analyses of complex diseases in association studies, we compare the procedure by Sobell et al. (Am J Med Genet 1993;48:28-35) with the adaptation of formal group sequential study designs by Pampallona and Tsiatis (J Stat Plan Inf 1994;42:19-35). Error rates and average sample sizes are investigated by Monte-Carlo simulations. RESULTS: Formal sequential designs have a higher power regardless of underlying genetic effects. In addition, compared with conventional designs with fixed samples, average sample sizes are reduced considerably; under the null hypothesis of no association, up to 50% of the required sample size can be spared. CONCLUSIONS: To increase the efficiency of genetic-epidemiological case-control studies, we recommend using formal group sequential study designs. The tremendous savings in average sample sizes are expected to affect both cost and time spent on large-scale studies.

Explore related subjects

Case-Control StudiesData Interpretation, StatisticalDiseaseEpidemiologyHumansMonte Carlo MethodJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Inke R König, Andreas Ziegler. 2003. Group sequential study designs in genetic-epidemiological case-control studies.. https://doi.org/10.1159/000073734

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Analysis of matched case-control data with multiple ordered disease states: possible choices and comparisons.

In an individually matched case-control study, effects of potential risk factors are ascertained through conditional logistic regression (CLR). Extension of CLR to situations with multiple disease or reference categories has been made through polychotomous CLR and is shown to be more efficient than carrying out separate CLRs for each subgroup. In this paper, we consider matched case-control studies where there is one control group, but there are multiple disease states with a natural ordering among themselves. This scenario can be observed when the cases can be further classified in terms of the seriousness or progression of the disease, for example, according to different stages of cancer. We explore several popular models for ordered categorical data in this context. We first adopt a cumulative logit or equivalently, a proportional-odds model to account for the ordinal nature of the data. The important distinction of this model from a stratified dichotomous and polychotomous logistic regression model is that the stratum-specific nuisance parameters cannot be eliminated in this model via the conditional-likelihood approach. We discuss a Mantel-Haenszel approach for analysing such data. We point out possible difficulties with standard likelihood-based approaches with the cumulative logit model when applied to case-control data. We then consider an alternative conditional adjacent-category logit model. We illustrate the methods by analysing data from a matched case-control study on low birthweight in newborns where infants are classified according to low and very low birthweight and a child with normal birthweight serves as a control. A simulation study compares the different ordinal methods with methods ignoring sub-classification of the ordered disease states.

Case-Control Studies↗
PubMed2007

No association between the Ser9Gly polymorphism of the dopamine D3 receptor gene and schizophrenia in a Spanish sample.

This study aims to further evaluate the controversial association between the Ser9Gly polymorphism in codon 9 of the D3 dopamine receptor gene (DRD3) and schizophrenia in psychiatric inpatients acutely hospitalized in two general hospitals in Madrid, Spain. The Ser9Gly polymorphism of the DRD3 was examined in 178 schizophrenic patients, 286 patients with other psychiatric diagnoses, and 132 controls recruited. Genotype frequencies were in Hardy-Weinberg equilibrium. No association was found between schizophrenia and the Ser9Gly polymorphism of the D3 dopamine receptor gene.

Case-Control Studies↗
PubMed2007

Fetal and maternal MTHFR C677T genotype, maternal folate intake and the risk of nonsyndromic oral clefts.

The association between maternal folate intake and risk of nonsyndromic oral clefts has been studied among many populations with conflicting results. The methylenetetrahydrofolate reductase gene (MTHFR) plays a major role in folate metabolism, and several polymorphisms, including C677T, are common in European populations. Data from a French study (1998-2001) let us investigate the roles of maternal dietary folate intake and the MTHFR polymorphism and their interaction on the risk of cleft lip with/without cleft palate (CL/P) and cleft palate only (CP). We used both case-control (164 CL/P, 76 CP, 236 controls; 148, 59, 168 of whom, respectively, had an available genotype) and case-parent (143 CL/P and 56 CP families) study designs and distinguished the role of the child's genotype and maternally mediated effects on risks. This study observed a beneficial effect of mothers' dietary folate intake on their offspring's risk (odds ratio (OR)(< or = 230 microg/day) = ref; for CL/P, OR([230-314 microg/day]) = 0.56, 95% confidence interval = 0.3-0.9, OR(>314 microg/day) = 0.64, 0.4-1.1; for CP, OR([230-314 microg/day]) = 1.15, 0.6-2.2, OR(>314 microg/day) = 0.70, 0.3-1.4). We observed a reduced risk associated with the TT genotype of the child in the case-control analysis (OR(CC) = ref; for CL/P, OR(TT) = 0.54, 0.3-1.1; for CP, OR(TT) = 0.33, 0.1-1.0); this genotype, either fetal or maternal, was not statistically significant in the case-parent analysis. A frequency of TT genotype higher in our control group than previously reported in France can partly explain the risk reduction observed in case-control comparison. Interactions were not statistically significant. Stratified case-parent analysis showed, however, slight heterogeneity in the role of TT genotype according to folate intake. The modest sample size limits this study, which nonetheless provides new estimate of the possible impact of dietary folate intake and MTHFR polymorphism on oral clefts.

Case-Control Studies↗