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bioRxiv · 10.1101/052670

Meta-analysis of 2,104 trios provides support for 10 novel candidate genes for intellectual disability

Stefan H. Lelieveld·Margot R.F. Reijnders·Rolph Pfundt·Helger G. Yntema·Erik-Jan Kamsteeg·Petra de Vries·Bert B.A. de Vries·Marjolein H. Willemsen·Tjitske Kleefstra·Katharina Löhner·Maaike Vreeburg·Servi Stevens·Ineke van der Burgt·Ernie M.H.F. Bongers·Alexander P.A. Stegmann·Patrick Rump·Tuula Rinne·Marcel R. Nelen·Joris A. Veltman·Lisenka E.L.M. Vissers·Han G. Brunner·Christian Gilissen
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Abstract

To identify novel candidate intellectual disability genes, we performed a meta-analysis on 2,637 de novo mutations, identified from the exomes of 2,104 ID trios. Statistical analyses identified 10 novel candidate ID genes, including DLG4, PPM1D, RAC1, SMAD6, SON, SOX5, SYNCRIP, TCF20, TLK2 and TRIP12. In addition, we show that these genes are intolerant to non-synonymous variation, and that mutations in these genes are associated with specific clinical ID phenotypes.

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Stefan H. Lelieveld, Margot R.F. Reijnders, Rolph Pfundt, Helger G. Yntema, Erik-Jan Kamsteeg, Petra de Vries, Bert B.A. de Vries, Marjolein H. Willemsen, Tjitske Kleefstra, Katharina Löhner, Maaike Vreeburg, Servi Stevens, Ineke van der Burgt, Ernie M.H.F. Bongers, Alexander P.A. Stegmann, Patrick Rump, Tuula Rinne, Marcel R. Nelen, Joris A. Veltman, Lisenka E.L.M. Vissers, Han G. Brunner, Christian Gilissen. 2016-05-11. Meta-analysis of 2,104 trios provides support for 10 novel candidate genes for intellectual disability. https://doi.org/10.1101/052670

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