Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing

Altres ajuts: This work was partly carried out on the Dutch national e-infrastructure with the support of the SURF Foundation. Barbara Franke and her team are supported by funding from a personal Vici grant of the Netherlands Organisation for Scientific Research (NWO; grant 016-130-669, to BF), [...]. In addition, this work was supported by the European College of Neuropsychopharmacology (ECNP Network "ADHD across the Lifespan"). Klaus-Peter Lesch and his team are supported by the Deutsche Forschungsgemeinschaft (DFG: CRU 125, CRC TRR 58 A1/A5), [...], Fritz Thyssen Foundation (No. 10.13.1185), ERA-Net NEURON/RESPOND, No. 01EW1602B, and 5-100 Russian Academic Excellence Project. [...]. The NBS exome chip data were generated in a research project that was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). The Heinz Nixdorf Recall (HNR) study is supported by the Heinz Nixdorf Foundation (Germany). Additionally, the study is funded by the German Ministry of Education and Science and the German Research Council (DFG; Project SI 236/8-1, SI236/9-1, ER 155/6-1). [...]. MR is a recipient of [...] and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. Jan Haavik and his team are supported by the K.G. Jebsen Foundation for Medical Research, University of Bergen, the Western Norwegian Health Authorities (Helse Vest). [...]. SC is supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e:Med Program (grant 01ZX1314A). He also receives support by the Swiss National Science Foundation (project no. 310030_156791). This publication was funded by the German Research Foundation (DFG) and the University of Wuerzburg in the funding programme Open Access Publishing. Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a complex genetic background, hampering identification of underlying genetic risk factors. We hypothesized that combining linkage analysis and whole-exome sequencing (WES) in multi-generation pedigrees with multiple affected individuals can point toward novel ADHD genes. Three families with multiple ADHD-affected members (N = 70) and apparent dominant inheritance pattern were included in this study. Genotyping was performed in 37 family members, and WES was additionally carrie