Premium
Sequential Designs for Genetic Epidemiological Linkage or Association Studies A Review of the Literature
Author(s) -
Böddeker Inke R.,
Ziegler Andreas
Publication year - 2001
Publication title -
biometrical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 63
eISSN - 1521-4036
pISSN - 0323-3847
DOI - 10.1002/1521-4036(200108)43:4<501::aid-bimj501>3.0.co;2-i
Subject(s) - linkage (software) , context (archaeology) , interim , computer science , sample size determination , genetic association , sample (material) , data mining , statistics , genetics , mathematics , biology , genotype , single nucleotide polymorphism , history , paleontology , chemistry , archaeology , chromatography , gene
Objectives . The cost of a genetic linkage or association study is largely determined by the number of individuals to be recruited, phenotyped, and genotyped. The efficiency can be increased by using a sequential procedure that reduces time and cost on average. Two strategies for sequential designs in genetic epidemiological studies can be distinguished: One approach is to increase the sample size sequentially and to conduct multiple significance tests on accumulating data. If significance or futility can be assumed with a certain probability, the study is stopped. Otherwise, it is carried on to the next stage. The second approach is to conduct early linkage analyses on a coarse marker grid, and to increase marker density in later stages. Interim analyses are performed to select interesting genomic areas for follow up. The aim of this article is to give a review on sequential procedures in the context of genetic linkage and association studies. Methods . A systematic literature search was performed in the Medline and the Linkage Bibliography databases. Articles were defined as relevant if a sequential design was proposed or applied in genetic linkage or association studies. Results . The majority of proposed study designs is developed to meet the demands of specific studies and lacks a theoretical foundation. A second group of procedures is based on simulation results and principally restricted to the specific simulated situations. Finally, some theoretically founded procedures have been proposed that are discussed in detail. Conclusions . Although interesting and promising procedures have been suggested, they still lack realizations for practical purposes. In addition, further developments are required to adapt sequential strategies for optimal use in genetic epidemiological studies.