Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
de Jong S., Diniz MJA., Saloma A., Gadelha A., Santoro ML., Ota VK., Noto C., Wray NR., Ripke S., Mattheisen M., Trzaskowski M., Byrne EM., Abdellaoui A., Adams MJ., Agerbo E., Air TM., Andlauer TFM., Bacanu SA., Bækvad-Hansen M., Beekman ATF., Bigdeli TB., Binder EB., Blackwood DHR., Bryois J., Buttenschøn HN., Bybjerg-Grauholm J., Cai N., Castelao E., Christensen JH., Clarke TK., Coleman JRI., Colodro-Conde L., Couvy-Duchesne B., Craddock N., Crawford GE., Davies G., Deary IJ., Degenhardt F., Derks EM., Direk N., Dolan CV., Dunn EC., Eley TC., Escott-Price V., Kiadeh FFH., Finucane HK., Forstner AJ., Frank J., Gaspar HA., Gill M., Goes FS., Gordon SD., Grove J., Hansen CS., Hansen TF., Herms S., Hickie IB., Hoffmann P., Homuth G., Horn C., Hottenga JJ., Hougaard DM., Ising M., Jansen R., Jones I., Jones LA., Jorgenson E., Knowles JA., Kohane IS., Kraft J., Kretzschmar WW., Krogh J., Kutalik Z., Li Y., Lind PA., MacIntyre DJ., MacKinnon DF., Maier RM., Maier W., Marchini J., Mbarek H., McGrath P., McGuffin P., Medland SE., Mehta D., Middeldorp CM., Mihailov E., Milaneschi Y., Milani L., Mondimore FM., Montgomery GW., Mostafavi S., Mullins N., Nauck M., Ng B., Nivard MG., Nyholt DR., Oskarsson H., Owen MJ., Painter JN.
© 2018, The Author(s). 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 ~ 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.