ENIGMA Plasticity

Working Group
Dr. Rachel Brouwer
UMC Utrecht

Dr. Hilleke Hulshoff-Pol
UMC Utrecht
ENIGMA’s Plasticity Working Group, currently lead by Rachel Brouwer and Hillele Hulshoff-Pol, is working to discover genomic loci that promote or mitigate brain tissue loss, with GWAS of brain change in 31 worldwide cohorts with longitudinal MRI (N > 5,000). Brain atrophy is associated with cognitive decline in old age, so finding genes driving brain tissue loss may identify genetic pathways involved in neurodegeneration. ENIGMA-Plasticity has already established heritability of global and subcortical brain changes (Brouwer 2017), in 5 longitudinal twin cohorts (BrainSCALE, QTIM, Utwins1, VETSA and OATS). Total brain, cerebellar and hippocampal changes, among others, were highly heritable, and separate genetic factors influenced brain change over time and baseline brain volumes, indicating the existence of genetic variants unique for brain plasticity. Our pilot work screened twin and pedigree data worldwide to prove feasibility (Brouwer 2017), and is mapping gene effects on tissue loss rates using our novel method, PyrPL.

QUESTIONS

If we combine a polygenic score for brain tissue loss, the epigenetic clock, and brain age, do they predict clinical decline better than any one metric?
Genetic variants associated with hippocampal volume. The most significant SNP within an associated locus is labeled. For the significant loci and age-dependent loci (Chromosome 19) we labeled the nearest gene, which is not necessarily the gene of action (Hibar 2017).
Heritability and Manhattan plot of genetic variation associated with subcortical brain volumes in in a partnership between the ENIGMA and CHARGE Consortia. The seven highlighted structures showed the highest heritability (Satizabal 2017)
Interview with R. Brouwer
For more info & how to join ENIGMA-Plasticity, click here.