Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

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 (Per Qvist and Preben Bo Mortensen, members of-)

AU - Mortensen, Preben Bo

AU - Qvist, Per

AU - Buttenschøn, Henriette Nørmølle

AU - Christensen, Jane Hvarregaard

AU - Grove, Jakob

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.

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UR - http://www.scopus.com/inward/record.url?scp=85061101811&partnerID=8YFLogxK

U2 - 10.1038/s42003-018-0155-y

DO - 10.1038/s42003-018-0155-y

M3 - Journal article

C2 - 30320231

SN - 2399-3642

VL - 1

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 163

ER -