Genome-wide meta-analyses of non-response to antidepressants identify novel loci and potential drugs.

Antidepressants exhibit a considerable variation in efficacy, and increasing evidence suggests that individual genetics contribute to antidepressant treatment response. Here, we combined data on antidepressant non-response measured using rating scales for depressive symptoms, questionnaires of treatment effect, and data from electronic health records, to increase statistical power to detect genomic loci associated with non-response to antidepressants in a total sample of 135,471 individuals prescribed antidepressants (25,255 non-responders and 110,216 responders). We performed genome-wide association meta-analyses, genetic correlation analyses, leave-one-out polygenic prediction, and bioinformatics analyses for genetically informed drug prioritization.

Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity.

Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability.

Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis.

Sex is an important covariate in all genetic and epigenetic research due to its role in the incidence, progression and outcome of many phenotypic characteristics and human diseases. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a sex bias towards higher incidence in males. Here, we report for the first time a blood-based epigenome-wide association study meta-analysis in 9274 individuals after stringent quality control (5529 males and 3975 females).