A common MECP2 haplotype associates with reduced cortical surface area in humans in two independent populations

作者：Joyner Alexander H; Roddey J Cooper; Bloss Cinnamon S; Bakken Trygve E; Rimol Lars M; Melle Ingrid; Agartz Ingrid; Djurovic Srdjan; Topol Eric J; Schork Nicholas J^*; Andreassen Ole A; Dale Anders M

来源：Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(36): 15483-15488.

DOI：10.1073/pnas.0901866106

• MRI
• neuroscience
• imaging genetics

The gene MECP2 is a well-known determinant of brain structure. Mutations in the MECP2 protein cause microencephalopathy and are associated with several neurodevelopmental disorders that affect both brain morphology and cognition. Although mutations in MECP2 result in severe neurological phenotypes, the effect of common variation in this genetic region is unknown. We find that common sequence variations in a region in and around MECP2 show association with structural brain size measures in 2 independent cohorts, a discovery sample from the Thematic Organized Psychosis research group, and a replication sample from the Alzheimer's Disease Neuroimaging Initiative. The most statistically significant replicated association (P < 0.025 in both cohorts) involved the minor allele of SNP rs2239464 with reduced cortical surface area, and the finding was specific to male gender in both populations. Variations in the MECP2 region were associated with cortical surface area but not cortical thickness. Secondary analysis showed that this allele was also associated with reduced surface area in specific cortical regions (cuneus, fusiform gyrus, pars triangularis) in both populations.

• 出版日期2009-9-8