Our findings have important implications for downstream investigations. One interpretation is that the nonspecific effects found through using minimal phenotyping approaches will still advance understanding of the biology of psychiatric disorders and their treatment5,57. A recent report used the ‘quasi-replication’ of GWAS loci between depressive symptoms and neuroticism as validation of their functional significance56. An alternative view is that these loci reflect the ways in which depressive symptoms can develop as secondary effects, including through susceptibility to adverse life events58, personality types24 and use of or exposure to psychoactive agents like cigarettes59,60—in which case, while useful for understanding the basis of mental ill health, they are not informative about the genetic etiology of MDD and are not useful for developing disease-specific treatment.
