Multivariate Genome-wide and integrated transcriptome and epigenome-wide analyses of the Well-being spectrum

Phenotypes related to well-being (life satisfaction, positive affect, neuroticism, and depressive symptoms), are genetically highly correlated (| r g | > .75). Multivariate genome-wide analyses ( N obs = 958,149) of these traits, collectively referred to as the well-being spectrum, reveals 63 significant independent signals, of which 29 were not previously identified. Transcriptome and epigenome analyses implicate variation in gene expression at 8 additional loci and CpG methylation at 6 additional loci in the etiology of well-being. We leverage an anatomically comprehensive survey of gene expression in the brain to annotate our findings, showing that SNPs within genes excessively expressed in the cortex and part of the hippocampal formation are enriched in their effect on well-being.