TY - JOUR
T1 - Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
AU - de Jong, Simone
AU - Diniz, Mateus Jose Abdalla
AU - Saloma, Andiara
AU - Gadelha, Ary
AU - Santoro, Marcos L
AU - Ota, Vanessa K
AU - Noto, Cristiano
AU - Curtis, Charles
AU - Newhouse, Stephen J
AU - Patel, Hamel
AU - Hall, Lynsey S
AU - O Reilly, Paul F
AU - Belangero, Sintia I
AU - Bressan, Rodrigo A
AU - Breen, Gerome
AU - Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium (Thomas Werge, Merete Nordentoft, Thomas F. Hansen, Wesley Thompson, Shantel Marie Weinsheimer (Members))
A2 - Werge, Thomas Mears
A2 - Hansen, Thomas Folkmann
A2 - Thompson, Wesley Kurt
A2 - Weinsheimer, Shantel Marie
A2 - Nordentoft, Merete
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1038/s42003-018-0155-y
DO - 10.1038/s42003-018-0155-y
M3 - Journal article
C2 - 30320231
SN - 2399-3642
VL - 1
SP - 163
JO - Communications biology
JF - Communications biology
ER -