Good news! Amazing stuff!
"An international collective of researchers is delivering new insights into why having multiple psychiatric disorders is the norm rather than the exception. In a study ... the team provides the largest and most detailed analysis to date on the genetic roots shared among 14 conditions. ..."
"... The majority of people diagnosed with a psychiatric disorder will ultimately be diagnosed with a second or third disorder in their lifetime, creating challenges for defining and treating these conditions. While a person’s environment and lived experience influence their risk for developing multiple disorders, their genetic makeup can also play a significant role.
By analyzing data from over 6 million individuals, the working group mapped the genetic landscape of 14 psychiatric conditions and revealed five families of disorders with high levels of genetic overlap. The results mark an important step toward understanding the genetic connections among psychiatric disorders and could ultimately help clinicians better serve their patients. ..."
"Psychiatric disorders display high levels of comorbidity and genetic overlap, challenging current diagnostic boundaries. For disorders for which diagnostic separation has been most debated, such as schizophrenia and bipolar disorder, genomic methods have revealed that the majority of genetic signal is shared.
While over a hundred pleiotropic loci have been identified by recent cross-disorder analyses, the full scope of shared and disorder-specific genetic influences remains poorly defined.
Here we addressed this gap by triangulating across a suite of cutting-edge statistical and functional genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders (1,056,201 cases).
Using genetic association data from common variants, we identified and characterized five underlying genomic factors that explained the majority of the genetic variance of the individual disorders (around 66% on average) and were associated with 238 pleiotropic loci.
The two factors defined by (1) Schizophrenia and bipolar disorders (SB factor); and (2) major depression, PTSD and anxiety (Internalizing factor) showed high levels of polygenic overlap and local genetic correlation and very few disorder-specific loci.
The genetic signal shared across all 14 disorders was enriched for broad biological processes (for example, transcriptional regulation), while more specific pathways were shared at the level of the individual factors.
The shared genetic signal across the SB factor was substantially enriched in genes expressed in excitatory neurons, whereas the Internalizing factor was associated with oligodendrocyte biology.
These observations may inform a more neurobiologically valid psychiatric nosology and implicate targets for therapeutic development designed to treat commonly occurring comorbid presentations."
Study reveals genetic overlap of 14 psychiatric disorders, explaining why patients often have multiple diagnoses (original news release) "Co-led by VCU expert Kenneth Kendler, a global research group has developed the most comprehensive genetic map to date, revealing five families of disorders with high levels of overlap."
Fig. 1: Genome-wide structural models.
a, Heatmap of rgs across the 14 disorders ... Disorders that load on the same factor are shown in the same colour. Per the legend at the bottom of the panel, darker blue shading indicates larger, positive rgs. LDSC estimates were used as the input to genomic SEM to produce the results in b and c. b, Estimates from the five-factor model along with standard errors in parentheses. Estimates are standardized relative to SNP-based heritabilities, where this is equal to the sum of the squared factor loading (the single-headed arrow(s) from the factor to the disorder) and the residual variance (the values on the double-headed arrows on the single-colour circles with text labels that begin with u). Disorders are shown as pie charts; the proportion of residual variance is shaded in purple and the variance explained by the psychiatric factors is shaded in the colour of the corresponding factor. c, Standardized estimates from the p-factor model. The disorders are colour coded as in b, and the first-order factors (F1–F5) are also colour coded to show variance explained by the second-order p-factor in yellow.
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