locus containing the myocyte enhancer factor 2C (MEF2C) and transmembrane protein 161B (TMEM161B) genes. Variants in MEF2C has been previously associated with multiple CNS phenotypes including epilepsy and intellectual disability8,9 and implicated in regulation of synaptic function10. TMEM161B, also brain-expressed, exhibits decreased levels of repressive dimethyl histone H3 Lys9/Lys27 methylation in response to social isolation in a mouse model of depression11. While Schizophrenia and Alzheimer’s Disease GWAS both identify the MEF2C region as a disease susceptibility locus, the peak schizophrenia and AD-associated SNPs are not in strong LD with the MDD SNP (Schizophrenia: rs18190012; r2=0.001 Alzheimer’s disease: rs190982, r2=0.016). Using a population prevalence of 15% for MDD estimated by the PGC Consortium13, we calculated heritability using LD score regression of h2liab=0.0528 for this dataset. When using the 23andMe MDD observed population prevalence of 25%, this results in h2liab=0.0612.
