期刊
COMMUNICATIONS BIOLOGY
卷 1, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s42003-018-0155-y
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资金
- FAPESP [2014/50830-2, 2010/08968-6]
- Marie Curie International Research Staff Exchange [FP7-PEOPLE-2011-IRSES/295192]
- National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
- European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant [IF 658195]
- National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre
- Medical Research Council
- Arthritis Research UK
- British Heart Foundation
- Cancer Research UK
- Chief Scientist Office
- Economic and Social Research Council
- Engineering and Physical Sciences Research Council
- National Institute for Health Research
- National Institute for Social Care and Health Research
- Wellcome Trust [MR/K006584/1]
- NATIONAL INSTITUTE OF MENTAL HEALTH [U01MH109536] Funding Source: NIH RePORTER
- MRC [G0401207, G0200243] Funding Source: UKRI
Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n similar to 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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