Discovery of genes that affect human brain connectivity: a genome-wide analysis of the connectome.

DISCOVERY OF GENES THAT AFFECT HUMAN BRAIN CONNECTIVITY: A GENOME-WIDE ANALYSIS OF THE CONNECTOME. Proc IEEE Int Symp Biomed Imaging. 2012;:542-545 Authors: Jahanshad N, Hibar DP, Ryles A, Toga AW, McMahon KL, de Zubicaray GI, Hansell NK, Montgomery GW, Martin NG, Wright MJ, Thompson PM Abstract Human brain connectivity is disrupted in a wide range of disorders - from Alzheimer's disease to autism - but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high angular resolution diffusion imaging (105-gradient HARDI). Using whole brain HARDI tractography, we extracted a relatively sparse 70×70 matrix representing fiber density between all pairs of cortical regions automatically labeled in co-registered anatomical scans. Additive genetic factors accounted for 1-58% of the variance in connectivity between 90 (of 122) tested nodes. We discovered genome-wide significant associations between variants and connectivity. GWAS permutations at various levels of heritability, and split-sample replication, validated our genetic findings. The resulting genes may offer new leads for mechanisms influencing aberrant connectivity and neurodegeneration. PMID: 22903411 [PubMed - as supplied by publisher]
Source: Proceedings - International Symposium on Biomedical Imaging - Category: Radiology Tags: Proc IEEE Int Symp Biomed Imaging Source Type: research