4.7 Article

A polygenic p factor for major psychiatric disorders

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TRANSLATIONAL PSYCHIATRY
卷 8, 期 -, 页码 -

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DOI: 10.1038/s41398-018-0217-4

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资金

  1. UK Medical Research Council [MR/M021475/1]
  2. US National Institutes of Health [AG046938]
  3. European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) [602768]
  4. European Research Council [295366]
  5. MRC/IoPPN Excellence Award
  6. National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
  7. MRC [MR/P005918/1, G0901245, G19/2, MR/M021475/1] Funding Source: UKRI
  8. NATIONAL INSTITUTE ON AGING [R01AG046938] Funding Source: NIH RePORTER

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It has recently been proposed that a single dimension, called the p factor, can capture a person's liability to mental disorder. Relevant to the p hypothesis, recent genetic research has found surprisingly high genetic correlations between pairs of psychiatric disorders. Here, for the first time, we compare genetic correlations from different methods and examine their support for a genetic p factor. We tested the hypothesis of a genetic p factor by applying principal component analysis to matrices of genetic correlations between major psychiatric disorders estimated by three methods family study, genome wide complex trait analysis, and linkage disequilibrium score regression and on a matrix of polygenic score correlations constructed for each individual in a UK-representative sample of 7 026 unrelated individuals. All disorders loaded positively on a first unrotated principal component, which accounted for 57, 43, 35, and 22% of the variance respectively for the four methods. Our results showed that all four methods provided strong support for a genetic p factor that represents the pinnacle of the hierarchical genetic architecture of psychopathology.

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