TY - JOUR T1 - Mapping the genetics of neuropsychological traits to the molecular network of the human brain using a data integrative approach JF - bioRxiv DO - 10.1101/336776 SP - 336776 AU - Afsheen Yousaf AU - Eftichia Duketis AU - Tomas Jarczok AU - Michael Sachse AU - Monica Biscaldi AU - Franziska Degenhardt AU - Stefan Herms AU - Sven Cichon AU - Sabine.M. Klauck AU - Jörg Ackermann AU - Christine M. Freitag AU - Andreas G. Chiocchetti AU - Ina Koch Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/06/03/336776.abstract N2 - Motivation Complex neuropsychiatric conditions including autism spectrum disorders are among the most heritable neurodevelopmental disorders with distinct profiles of neuropsychological traits. A variety of genetic factors modulate these traits (phenotypes) underlying clinical diagnoses. To explore the associations between genetic factors and phenotypes, genome-wide association studies are broadly applied. Stringent quality checks and thorough downstream analyses for in-depth interpretation of the associations are an indispensable prerequisite. However, in the area of neuropsychology there is no framework existing, which besides performing association studies also affiliates genetic variants at the brain and gene network level within a single framework.Results We present a novel bioinformatics approach in the field of neuropsychology that integrates current state-of-the-art tools, algorithms and brain transcriptome data to elaborate the association of phenotype and genotype data. The integration of transcriptome data gives an advantage over the existing pipelines by directly translating genetic associations to brain regions and developmental patterns. Based on our data integrative approach, we identify genetic variants associated with Intelligence Quotient (IQ) in an autism cohort and found their respective genes to be expressed in specific brain areas.Conclusion Our data integrative approach revealed that IQ is related to early down-regulated and late up-regulated gene modules implicated in frontal cortex and striatum, respectively. Besides identifying new gene associations with IQ we also provide a proof of concept, as several of the identified genes in our analysis are candidate genes related to intelligence in autism, intellectual disability, and Alzheimer’s disease. The framework provides a complete extensive analysis starting from a phenotypic trait data to its association at specific brain areas at vulnerable time points within a timespan of four days.Availability and Implementation Our framework is implemented in R and Python. It is available as an in-house script, which can be provided on demand.Contact afsheen.yousaf{at}kgu.de ER -