The genotype at that locus was also nominally associated with expression levels of the positional candidate gene TESC in adult human temporal lobe tissue, based on the UCL database of brain tissue resected during epilepsy surgeries. TESC is currently not well studied, but it is known that it is expressed during brain development in mice and chickens (Bao et al. 2009). It encodes tescalcin, which interacts with the Na+/H+ exchanger (NHE1) (Baumgartner et al. 2004), important in the regulation of intracellular pH, cell volume and cytoskeletal organization. In addition, intracranial volume was significantly associated with a variant (rs10784502) in the HMGA2 gene that had been previously tied to height. The CHARGE consortium had focused on elderly cohorts recruited primarily for studies of cardiovascular health in old age, whereas ENIGMA had aggregated data from cohorts across the lifespan showing the genetic effect was strong, happening over multiple stages of brain growth. Both efforts had strengths—the number of cohorts in ENIGMA (23) was larger than that of CHARGE, but some of the constituent cohorts in CHARGE numbered over 2,800 individuals.
