Analysis of shared heritability in common disorders of the brain
Анализ общей наследуемости распространённых заболеваний головного мозга
2018-06-21
SCID: 54.1/k6gxmee8
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brain disordersdiagnostic misclassificationgenetic correlationsgenome-wide association studiesshared heritability
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Abstract (AI)
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
Key Findings
1
Psychiatric disorders showed substantial common-variant risk sharing, whereas neurological disorders were genetically more distinct from one another and from psychiatric disorders.
2
Significant genetic sharing was identified between brain disorders and multiple brain-related phenotypes, including cognitive measures, across 1,191,588 individuals.
3
Simulations demonstrated that statistical power, diagnostic misclassification, and phenotypic heterogeneity can influence estimated genetic correlations.
4
The findings support common genetic variation as an important risk factor and heritability-based methods as useful tools for studying brain-disorder etiology.
5
The study quantified genetic sharing across 25 brain disorders using genome-wide association data from 265,218 patients and 784,643 controls.
Research Object
Common brain disorders (25 disorders) and related brain phenotypes analyzed for genetic sharing using genome-wide association study data
Research Subject
Shared common-variant genetic risk and heritability-based relationships among brain disorders and phenotypes, including the effects of diagnostic misclassification and phenotypic heterogeneity
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2018-06-21
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