Publications by authors named "A M den Harder"

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.

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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.

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Secure residential care (SRC) is criticized for several reasons. Therefore, in many countries, the general policy is to limit the length of stay of adolescents in SRC. However, research on length of stay and treatment effects of SRC on adolescents' behavioral problems is sparse.

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Ancient whole-genome duplications are believed to facilitate novelty and adaptation by providing the raw fuel for new genes. However, it is unclear how recent whole-genome duplications may contribute to evolvability within recent polyploids. Hybridization accompanying some whole-genome duplications may combine divergent gene content among diploid species.

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Wild populations are increasingly threatened by human-mediated climate change and land use changes. As populations decline, the probability of inbreeding increases, along with the potential for negative effects on individual fitness. Detecting and characterizing runs of homozygosity (ROHs) is a popular strategy for assessing the extent of individual inbreeding present in a population and can also shed light on the genetic mechanisms contributing to inbreeding depression.

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