Boerglum, A. D. | bioRxiv Science

bioRxiv2018

Does Neuroticism Cause Depression? A Mendelian Randomization Study

Neuroticism is a heritable personality trait, characterized by negative emotions such as worrying, feelings of guilt, loneliness and being easily hurt. Increased levels of neuroticism are associated with poor mental health - development of depression in particular - but it remains uncertain whether this association represents a causal effect [1]. Here, we use Mendelian randomization (MR) to investigate whether neuroticism is a causal risk factor for development of depression.\n\nMR is an analytic approach to assess the causality of an observed association between a risk factor and a clinically relevant outcome [2]. MR is particularly useful in situations where randomized controlled trials are not possible and observational studies provide biased associations because of confounding or reverse causality. MR uses genome-wide association study (GWAS) data to identify instrumental variables (single nucleotide polymorphisms; SNPs) for a risk f ...

genetics↗

bioRxiv2017

A genome-wide association study for shared risk across major psychiatric disorders in a nation-wide birth cohort implicates fetal neurodevelopment as a key mediator

There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here, we leverage the unique iPSYCH study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder SNP-heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during midgestation. This epoch is supported by partitioning cross-disorder SNP-heritability which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings indicate that dysregulation of genes that direct neurodevelopment by common genetic variants results in general liability for many later psychiatric outcomes.

genetics↗