dr. S. (Roula) Tsonaka



  • models for longitudinal omics
  • RNAseq
  • analysis of clustered data (e.g. families)
  • genetic association studies: gene-set/pathway-based analyses


I am an Assistant Professor at the Department of Medical Statistics and Bioinformatics of the Leiden University Medical Centre. I obtained my PhD in Biostatistics from the Leuven Biostatistics and statistical Bioinformatics Centre of the Catholic University Leuven in Belgium.

My research interests focus on the developement of novel statistical methodology and software for the analysis of correlated data structures, such as longitudinal and clustered data, with applications in clinical and genomics studies. In the area of statistical genetics my research has focused on the development of multimarker association tools for candidate-gene and genome-wide association studies, pathway-based analysis and analysis of family-based studies in genetics. In the area of correlated data analysis, I have focused on the development of methods to handle non-ignorable dropout in follow-up clinical trials and diagnostic tools to assess modelling assumptions of mixed-effects models.





PhD in Mathematics (2004 - 2008): Leuven Biostatistics and statistical Bioinformatics Centre Catholic University Leuven, Belgium

MSc in Statistics (2002 - 2003): Department of Statistics, Athens University of Economics and Business, Greece

Bachelor in Statistics (1998 - 2002): Department of Statistics, Athens University of Economics and Business, Greece


A complete list of my publications can be found at:

Google Scholar 




Methodological papers


Tissier, R., Tsonaka, R. Mooijaart, S.P., Slagboom, E., and Houwing-Duistermaat, J.J. (2017). Secondary phenotype analysis in ascertained family designs: Application to the Leiden Longevity Study. Statistics in Medicine, 36(14), 2288 - 2301.

Tsonaka, R., van der Woude, D. and Houwing-Duistermaat, J. (2015). Marginal genetic effects estimation in family and twin studies using random-effects models. Biometrics, 71, 1130 - 1138.

Balliu, B., Tsonaka, R., Bohringer, S. and Houwing-Duistermaat, J. (2015). A Retrospective Likelihood Approach for Efficient Integration of Multiple Omics Factors in Case-Control Association Studies. Genetic Epidemiology, 39, 156 - 165.

Tissier, R., Uh, H.W., van den Akker, E., Balliu, B., Tsonaka, R., Houwing-Duistermaat, J.J. (2015). Gene co-expression network analysis for family studies based on a meta-analytic approach. BMC Proceedings. 

Houwing-Duistermaat, J.J., Helmer, Q., Balliu, B., van den Akker E., Tsonaka, R., Uh, H.W. (2014). Gene analysis for longitudinal family data using random-effects models. BMC Proceedings, 8(Suppl 1):S88.

Balliu, B., Uh, H.W., Tsonaka, R., Boehringer, S., Helmer, Q., Houwing-Duistermaat J.J. (2014). Combining information from linkage and association mapping for next generation sequencing longitudinal family data. BMC Proceedings. 8(Suppl 1):S34.

Tsonaka, R., de Visser, M., Houwing-Duistermaat, J. (2012). Estimation of genetic effects in multiple cases family studies using penalized maximum likelihood methodology, Biostatistics, 14, 220 - 231. 

Balliu, B., Tsonaka, R., van der Woude, D., Boehringer, S., Houwing-Duistermaat, J.J. (2012). Combining family and twin data in association studies to estimate the non-inherited maternal antigens effect. Genetic Epidemiology, 36, 811 - 819.

Tsonaka, R., van der Helm - Mil, A., Houwing-Duistermaat, J. (2012). A two-stage mixed-effects model approach for gene-set analyses in candidate gene studies. Statistics in Medicine, 13, 1190 – 1202.

Houwing-Duistermaat, J., Uh, H.-W. and Tsonaka, R. (2011). Pathway Analysis for Family Data using Nested Random Effects Models. BMCProceedings, 5(Suppl 9):S22 .

Uh, H.-W., Tsonaka, R. and Houwing-Duistermaat, J. (2011). Does gene set analysis facilitate for common variants to tag rare ones? BMC Proceedings,5(Suppl 9):S90.

Tsonaka, R., Rizopoulos, D., Verbeke, G. and Lesaffre, E. (2010). Non-ignorable models for intermittently missing categorical longitudinal responses. Biometrics,66, 834 - 844.

Tsonaka, R., Verbeke, G. and Lesaffre, E. (2009). A semi-parametric shared parameter model to handle non-monotone non-ignorable missingness. Biometrics, 65, 81 - 87.

Lesaffre, E., Rizopoulos, D. and Tsonaka, R. (2007). The logistic-transform for bounded outcome scores. Biostatistics, 8, 72 - 85.

Tsonaka, R. and Moustaki, I. (2007). Parameter constraints in generalized linear latent variable models. Computational Statistics & Data Analysis, 51, 4164 - 4177.

Tsonaka, R., Rizopoulos, D. and Lesaffre, E. (2006). Power and sample size calculations for discrete bounded outcome scores. Statistics in Medicine, 25, 4241 - 4252.





Collaborative Research 

van Nies, J.A., Tsonaka, R., Gaujoux-Viala, C., Fautrel, B., van der Helm-van Mil, A.H. (2015). Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden Early Arthritis Clinic and ESPOIR cohorts. Annals of the Rheumatic Diseases, 74, 806 - 812.

van Steenbergen, H.W., Tsonaka, R.,  Huizinga, T.W.J., le Cessie, S., van der Helm-van Mil, A.H.M. (2015). Predicting the severity of joint damage in Rheumatoid Arthritis; the contribution of genetic factors, Annals of the Rheumatic Diseases. 74, 876 - 882.

de Rooy, D.P.C., Tsonaka, R., Andersson, M.L.E., Zhernakova, A., de Kovel, C.G., Koeleman, B.P.C., van der Heijde, D.M.F.M., Huizinga, T.W.J., Toes, R.E.M., Houwing-Duistermaat, J.J., Svensson, B., van der Helm-van Mil, A.H.M. (2015). Genetic Factors for the Severity of ACPA-negative Rheumatoid Arthritis in 2 Cohorts of Early Disease: A Genome-wide Study. The Journal of Rheumatology, 42, 1383 - 1391.

van Steenbergen, H. W., Tsonaka, R., Huizinga, T. W., van der Helm-van Mil, A. H. (2014). Fatigue in rheumatoid arthritis: a persistent problem: a large longitudinal study. RMD Open 2015, 1:e000041, doi:10.1136/rmdopen-2014-000041.

Knevel, R., de Rooy, D.P.C., Saxne, T., Lindqvist, E., Leijsma, M.K., Daha, N.A., Koeleman, B.P.C.,  Tsonaka, R., Houwing-Duistermaat, J.J., Schonkeren, J.J.M., Toes, R.E.M., Huizinga, T.W.J., Brouwer, E., Wilson, A.G., van der Helm-van Mil, A.H.M. (2014). Genetic variants in OPG are associated with progression of joint destruction in Rheumatoid Arthritis, Arthritis Research & Therapy, 16:R108.

Almouzni, G., Altucci, L., Amati, B., Ashley, N., Baulcombe, D., Beaujean, N., Bock, C., Bongcam-Rudloff, E., Bousquet, J., Braun, S., Bressac-de Paillerets, B., Bussemakers, M., Clarke, L., Conesa, A., Estivill, X., Fazeli, A., Grgurevic', N., Gut, I., Heijmans, B.T., Hermouet, S., Houwing–Duistermaat, J., Iacobucci, I., Ilaš, J., Kandimalla, R., Krauss-Etschmann, S., Lasko, P., Lehmann, S., Lindroth, A., Majdic, G., Marcotte, E., Martinelli, G., Martinet, N., Meyer, E., Miceli, C., Mills, K., Moreno-Villanueva, M., Morvan, G., Nickel, D., Niesler, B., Nowacki, M., Nowak, J., Ossowski, S., Pelizzola, M., Pochet, R., Potocnik, U., Radwanska, M., Raes, J., Rattray, M., Robinson, M.D., Roelen, B., Sauer, S., Schinzer, D., Slagboom, E., Spector, T., Stunnenberg, H.G., Tiligada, E., Torres-Padilla, M., Tsonaka, R., Van Soom, A., Vidakovic', M., Widschwendter, M. (2014). Relationship between genome and epigenome - challenges and requirements for future research, BMC Genomics, 15(1): 487.

Wiria, A., Hamid, F., Wammes, L., Kaisar, M., May, L., Prasetyani, M., Wahyuni, S., Djuardi, Y., Ariawan, I., Wibowo, H., Lell, B., Sauerwein, R., Brice, G., Sutanto, I., van Lieshout, L., de Craen, A., van Ree, R., Verweij, J., Tsonaka, R., Houwing, J., Luty, A., Sartono, E., Supali, T., Yazdanbakhsh, M. (2013). The effect of three-monthly albendazole treatment on malarial parasitemia and allergy: a household-based cluster-randomized, PLOS One, To appear. 

de Rooy, D., Yeremenko, N., Knevel, R., Lindqvist, E., Saxne, T., Krabben, A., Leijsma, M., Daha, N., Tsonaka, R., Zhernakova, S., Houwing-Duistermaat, J.J., Huizinga, T.W.J., Toes, R., Baeten, D., Brouwer, E., van der Helm-van Mil, A. (2012). Genetic studies on components of the Wnt signaling pathway and the severity of joint destruction in Rheumatoid Arthritis. Annals of the Rheumatic Diseases, To appear.

Knevel, R., Tsonaka, R., le Cessie, S., van der Linden, M.P.M, Huizinga, T.W.J., van der Heijde, D.M.F.M., Houwing-Duistermaat, J.J., van der Helm-van Mil, A.H.M. (2012). Comparison of methodology to analyze associations between risk factors and progression of joint destruction in Rheumatoid Arthritis in longitudinal studies. Scandinavian Journal of Rheumatology, To appear.

Knevel, R., Krabben, A., Brouwer, E., Posthumus, M.D., Wilson, A.G., Saxne, T., Lindqvist, E., de Rooy, D.P.C., Daha, N.A., van der Linden, M.P.M., Stoeken-Rijsbergen, G., van Toorn, L., Tsonaka, S., Zhernakova, A., Houwing-Duistermaat, J.J., Toes, R., Huizinga, T.W.J., van der Helm-van Mil, A.H.M. (2012). Genetic variants in IL-15 Associate with Progression of Joint Destruction in Rheumatoid Arthritis, a Multi Cohort Study. Annals of the Rheumatic Diseases. To appear.

Knevel, R., de Rooy, D.P, Gregersen, P.K., Lindqvist, E., Wilson, A.G., Gröndal, E. G. Zhernakova, A., van Nies, J., Toes, R.E., Tsonaka, R., Houwing-Duistermaat, J.J., Steinberg, S., Kárason, A., Steinsson, K., Huizinga, T.W., Saxne, T., van der Helm-van Mil, A.H. (2012). Studying associations between variants in TNFAIP3-OLIG3 and TRAF1-C5 and the progression of joint destruction in rheumatoid arthritis in multiple cohorts. Annals of Rheumatic Diseases, doi: 10.1136/annrheumdis-2012-201289.

Van de Voorde, P., Sabbe, M., Tsonaka, R., Rizopoulos, D., Calle, P., De Jaeger, A., Lesaffre, E., Matthys, D. (2010). The long-term outcome after severe trauma of children in Flanders (Belgium): a population-based cohort study using the International Classification of Functioning - related Outcome Score. European Journal of Pediatrics, 170, 65 - 73.

Van de Voorde, P., Sabbe, M., Calle, P., Lesaffre, E., Rizopoulos, D., Tsonaka, R., Christiaens, D., Vantomme, A., De Jaeger, A. and Matthys, D. (2008). Pediatric trauma and trauma care in Flanders (Belgium). Methodology and first descriptive results of the PENTA registry. European Journal of Pediatrics, 167, 1239 - 1249.

Van de Voorde, P., Sabbe, M., Rizopoulos, D., Tsonaka, R., de Jaeger, A., Lesaffre, E. and Peters, M. (2008). Assessing the level of consciousness in children: a plea for the Glasgow Coma Motor Subscore. Resuscitation, 76, 175 - 179.

Van de Werf, F. et al. (2006). Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomized trial. Lancet,367 (9510), 569 - 578.


Leids Universitair Medisch Centrum
Gebouw 2
Kamer S-05-042

Einthovenweg 20
2333 ZC Leiden
Tel: 071 5269722

Postzone S5-P
Postbus 9600
2300 RC Leiden

E-mail: S.Tsonaka@lumc.nl