DISCOVERY OF GENES THAT AFFECT HUMAN BRAIN CONNECTIVITY: A GENOME-WIDE ANALYSIS OF THE CONNECTOME.
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.
Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, CA.
Neda
N
Jahanshad
Derrek P
DP
Hibar
April
A
Ryles
Arthur W
AW
Toga
Katie L
KL
McMahon
Greig I
GI
de Zubicaray
Narelle K
NK
Hansell
Grant W
GW
Montgomery
Nicholas G
NG
Martin
Margaret J
MJ
Wright
Paul M
PM
Thompson