Use of support vector machines for disease risk prediction in genome-wide association studies: Concerns and opportunities

Florian Mittag, Finja Büchel, Mohamad Saad, Andreas Jahn, Claudia Schulte, Zoltan Bochdanovits, Javier Simón-Sánchez, Mike A. Nalls, Margaux Keller, Dena G. Hernandez, J. Raphael Gibbs, Suzanne Lesage, Alexis Brice, Peter Heutink, Maria Martinez, Nicholas W. Wood, John Hardy, Andrew B. Singleton, Andreas Zell, Thomas GasserManu Sharma

Research output: Contribution to journalArticle

24 Citations (Scopus)


The success of genome-wide association studies (GWAS) in deciphering the genetic architecture of complex diseases has fueled the expectations whether the individual risk can also be quantified based on the genetic architecture. So far, disease risk prediction based on top-validated single-nucleotide polymorphisms (SNPs) showed little predictive value. Here, we applied a support vector machine (SVM) to Parkinson disease (PD) and type 1 diabetes (T1D), to show that apart from magnitude of effect size of risk variants, heritability of the disease also plays an important role in disease risk prediction. Furthermore, we performed a simulation study to show the role of uncommon (frequency 1-5%) as well as rare variants (frequency <1%) in disease etiology of complex diseases. Using a cross-validation model, we were able to achieve predictions with an area under the receiver operating characteristic curve (AUC) of ∼0.88 for T1D, highlighting the strong heritable component (∼90%). This is in contrast to PD, where we were unable to achieve a satisfactory prediction (AUC ∼0.56; heritability ∼38%). Our simulations showed that simultaneous inclusion of uncommon and rare variants in GWAS would eventually lead to feasible disease risk prediction for complex diseases such as PD. The used software is available at

Original languageEnglish
Pages (from-to)1708-1718
Number of pages11
JournalHuman Mutation
Issue number12
Publication statusPublished - 1 Dec 2012
Externally publishedYes



  • Disease risk prediction
  • Genome-wide association studies
  • Machine learning
  • Parkinson disease
  • Support vector machines

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Mittag, F., Büchel, F., Saad, M., Jahn, A., Schulte, C., Bochdanovits, Z., Simón-Sánchez, J., Nalls, M. A., Keller, M., Hernandez, D. G., Gibbs, J. R., Lesage, S., Brice, A., Heutink, P., Martinez, M., Wood, N. W., Hardy, J., Singleton, A. B., Zell, A., ... Sharma, M. (2012). Use of support vector machines for disease risk prediction in genome-wide association studies: Concerns and opportunities. Human Mutation, 33(12), 1708-1718.