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Microarray- and Sequencing Studies

Statistical Methods for the Assessment of Genetic Variants in Microarray and Sequencing Studies

From 2012 to 2017, we have conducted the project "Statistical Methods for the Assessment of Genetic Variants in Microarray and Sequencing Studies" founded by the undefined Deutsche Forschungsgemeinschaft.

Goals of the Project

Variations in the human genome can substantially influence the risk of developing a disease. Therefore, numerous genetic association studies are concerned with single nucleotide polymorphisms (SNPs), the most common type of such genetic variants. While huge prespecified subsets of all SNPs in the genome can be measured with microarrays, the latest developments in biotechnology enable the sequencing of the whole genome or specific DNA regions, and hence, the measurement of all known SNPs in these regions as well as the detection of previously unknown, often rarely occurring genetic variants. When testing these SNPs for association with disease, typically only the form/genotype of the SNP is considered, although much more information exists for each SNP.

The major goal of this research group was to develop statistical procedures for the most common types of association studies that allow the inclusion of all available information on the SNPs from the study at hand and from previous studies, which might lead to a better assessment of the effect of a SNP on the disease risk. Further goals were to devise statistical methods for the detection of complex combinations of (common) SNPs and rare variants associated with disease in studies (such as exome sequencing studies) comprising tens of thousands of common and rare variants, and for the assessment of the joint effect of genetic variations belonging to the same gene as well as statistical procedures enabling an integrative analysis of SNPs and other types of genetic markers.


Liu, D., Schwender, H., Wang, M., Wang, H., Wang, P., Zhu, H., Zhou, Z., Li, J., Wu, T., Beaty, T.H.: Gene-Gene Interaction Between MSX1 and TP63 in Asian Case-Parent Trios with Nonsyndromic Cleft Lip with or without Cleft Palate. Birth Defects Research, DOI: 10.1002/bdr2.1139 (2018)

Wang, P., Wu, T., Schwender, H., Wang, H., Shi, B., Wang, Z., Yuan, Y., Liu, D., Wang, M., Li, J., Zhou, Z., Zhu, H., Beaty, T.H.: Evidence of Interaction Between Genes in the Folate/Homocysteine Metabolic Pathway in Controlling Risk of Nonsyndromic Oral Cleft. Oral Diseases, DOI: 10.1111/odi.12831 (2018)

Hüls, A., Krämer, U., Carlsten, C., Schikowski, T., Ickstadt, K., Schwender, H.: Comparison of Weighting Approaches for Genetic Risk Scores in Gene-Environment Interaction Studies. BMC Genetics, 18 p. 115 (2017)

Kaisers, W., Schwender, H., Schaal, H.: Sample Size Estimation for Detection of Splicing Events in Transcriptome Sequencing Data. International Journal of Molecular Sciences, 18 p. E1900 (2017)

Kaisers, W., Ptok, J., Schwender, H., Schaal, H.: Validation of Splicing Events in Transcriptome Sequencing Data. International Journal of Molecular Sciences, 18 p. E1110 (2017)

Kaisers, W., Boukamp, P., Stark, H.J., Schwender, H., Tigges, J., Krutmann, J., Schaal, H.: Age, Gender and UV-Exposition Related Effects on Gene Expression in In Vivo Aged Short Term Cultivated Human Dermal Fibroblasts. PLOS ONE, 12 p. e0175657 (2017)

Liu, D., Wang, H., Schwender, H., Marazita, M.L., Wang, Z., Yuan, Y., Wang, P., Liang, K.Y., Wu-Chou, Y.H., Wang, M., Shi, B., Zhu, H., Wu, T., Beaty T.H.: Gene-Gene Interaction of Single Nucleotide Polymorphisms in 16p13.3 may Contribute to the Risk of Non-Syndromic Cleft Lip with or without Cleft Palate in Chinese Case-Parent Trios. American Journal of Medical Genetics, Part A, 173 p. 1489-1494 (2017)

Schäfer, M., Klein, H.U., Schwender, H.: Integrative Analysis of Multiple Genomic Variables Using a Hierarchical Bayesian Model. Bioinformatics, 33 p. 3220-3227 (2017)

Xiao, Y., Taub, M.A., Ruczinski, I., Begum, F., Hetmanski, J.B., Schwender, H., Leslie, E.J., Koboldt, D.C., Murray, J.C., Marazita, M.L., Beaty, T.H.: Evidence for SNP-SNP Interaction Identified Through Targeted Sequencing of Cleft Case-Parent Trios. Genetic Epidemiology, 41 p. 244-250 (2017)

Klein, H.U., Schäfer, M.: Integrative Analysis of Histone ChIP-Seq and RNA-Seq Data. Current Protocols in Human Genetics, 90 p. 20.3.1-20.3.17 (2016)

Bu, L., Chen, Q., Wang, H., Zhang, T., Hetmanski, J.B., Schwender, H., Parker, M., Chou, Y.H., Yeow, V., Chong, S.S., Zhang, B., Jabs, E.W., Scott, A.F., Beaty, T.H.: Novel Evidence of Association with Nonsyndromic Cleft Lip with or without Cleft Palate was Shown for Single Nucleotide Polymorphisms in FOXF2 Gene in an Asian Population. Birth Defects Research A: Clinical and Molecular Teratology, 103 p. 857-862 (2015)

Casjens, S., Schwender, H., Brüning, T., Ickstadt, K.: A Novel Crossover Operator Based on Variable Importance for Evolutionary Multi-Objective Optimization with Tree Representation. Journal of Heuristics, 21 p. 1-24 (2015)

Gabdoulline, R., Kaisers, W., Gaspar, A., Meganathan, K., Doss, M.X., Jagtap, S., Hescheler, J., Sachinidis, A., Schwender, H.: Differences in the Early Development of Human and Mouse Embryonic Stem Cells. PLoS One, 10 p. e0140803 (2015)

Kaisers, W., Schaal, H., Schwender, H.: rbamtools: an R interface to samtools enabling fast accumulative tabulation of splicing events over multiple RNA-seq samples. Bioinformatics, 31 p. 1663-1664 (2015)

Younkin, S.G., Scharpf, R.B., Schwender, H., Parker, M.M., Scott, A.F., Marazita, M.L., Beaty, T.H., Ruczinski, I.: A Genome-Wide Study of Inherited Deletions Identified two Regions Associated with Nonsyndromic Isolated Oral Clefts. Birth Defects Research Part A: Clinical and Molecular Teratology, 103 p. 276-283 (2015)

Chen, Q., Wang, H., Schwender, H., Zhang, T., Hetmanski, J.B., Wu-Chou, Y.H., Ye, X., Yeow, V., Chong, S.S., Zhang, B., Jabs, E.W., Parker, M.M., Scott, A.F., Beaty, T.H.: Joint Testing of Genotypic and Gene-Environment Interaction Identified Novel Association for BMP4 with Non-Syndromic CL/P in an Asian Population Using Data from an International Cleft Consortium. PLoS One, 9 p. e109038 (2014)

Herrmann, S., Schwender, H., Ickstadt, K., Müller, P.: A Bayesian Changepoint Analysis of ChIP-Seq Data of Lamin B. Biochimica et Biophysica Acta, 1844 p. 138-144 (2014)

Klein, H.U., Schäfer, M., Porse, B.T., Hasemann, M.S., Ickstadt, K., Dugas, M.: Integrative Analysis of Histone ChIP-seq and Transcription Data Using Bayesian Mixture Models. Bioinformatics, 30 p. 1154-1162 (2014)

Malina, M., Ickstadt, K., Schwender, H., Posch, M., Bogdan, M.: Detection of Epistatic Effects with Logic Regression and a Classical Linear Regression Model. Statistical Applications in Genetics and Molecular Biology, 13 p. 83-104 (2014)

Neumann, C., Taub, M.A., Younkin, S.G., Beaty, T.H., Ruczinski, I., Schwender, H.: Analytic Power and Sample Size Calculation for the Genotypic Transmission/Disequilibrium Test in Case-Parent Trio Studies. Biometrical Journal, 68 p. 766-773 (2014)

Schwender, H., Li, Q., Neumann, C., Taub, M.A., Younkin, S.G., Berger, P., Scharpf, R.B., Beaty, T.H., Ruczinski, I.: Detecting Disease Variants in Case-Parent Trio Studies Using the Bioconductor Software Package trio. Genetic Epidemiology, 38 p. 516-522 (2014)

Wu, T., Schwender, H., Ruczinski, I., Murray, J.C., Marazita, M.L., Munger, R.G., Hetmanski, J.B., Parker, M.M., Wang, P., Murray, T., Taub, M., Li, S., Redett, R.J., Fallin, M.D., Liang, K.Y., {Wu-Chou}, Y.H., Chong, S.S., Yeow, V., Ye, X., Wang, H., Huang, S., Jabs, E.W., Shi, B., Wilcox, A.J., Jee, S.H., Scott, A.F., Beaty, T.B.: Evidence of Gene-Environment Interaction for two Genes on Chromosome 4 and Environmental Tabacco Smoke in Controlling the Risk of Nonsyndromic Cleft Palate. PLoS One, 9 p. e88088 (2014)

Younkin, S.G., Scharpf, R.B., Schwender, H., Parker, M.M., Scott, A.F., Marazita, M.L., Beaty, T.H., Ruczinski, I.: A Genome-Wide Study of De Novo Deletions Identifies a Candidate Locus for Non-Syndromic Isolated Cleft Lip/Palate Risk. BMC Genetics, 15 p. 24 (2014)

Beaty, T.H., Taub, M.A., Scott, A.F, Murray, J.C., Marazita, M.L., Schwender, H., Parker, M.M., Hetmanski, J.B., Balakrishnan, P., Mansilla, M.A., Mangold, E., Ludwig, K.U., Noethen, M.M., Rubini, M., Elcioglu, N., Ruczinski, I.: Confirming Genes Influencing Risk to Cleft Lip with/without Cleft Palate in a Case-Parent Trio Study. Human Genetics, 132 p. 771-781 (2013)

Li, Q., Schwender, H., Louis, T.A., Fallin, M.D., Ruczinski, I.: Efficient Simulation of Epistatic Interactions in Case-Parent Trios. Human Heridity, 75 p. 12-22 (2013)

Taub, M.A., Schwender, H.R., Younkin, S.G., Louis, T.A., Ruczinski, I.: On Multi-Marker Tests for Association in Case-Control Studies. Frontiers in Genetics, 4 p. 252 (2013)

Scharpf, R.B., Beaty, T.H., Schwender, H., Younkin, S.G., Scott, A.F., Ruczinski, I.: Fast Detection of De Novo Copy Number Variants from SNP Arrays for Case-Parent Trios. BMC Bioinformatics, 13 p. 330 (2012)

Schwender, H.: Imputing Missing Genotypes with Weighted K Nearest Neighbors. Journal of Toxicology and Environmental Health, Part A, 75 p. 438-446 (2012)

Schwender, H., Selinski, S., Blaszkewicz, M., Marchan, R., Ickstadt, K., Golka, K., Hengstler, J.G.: Distinct SNP Combinations Confer Susceptibility to Urinary Bladder Cancer in Smokers and Non-Smokers. PLoS ONE, 7 p. e51880 (2012)

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