PuSH - Publikationsserver des Helmholtz Zentrums München

Dybdahl Krebs, M.* ; Georgii Hellberg, K.L.* ; Lundberg, M.* ; Appadurai, V.* ; Ohlsson, H.* ; Pedersen, E.S.L.* ; Steinbach, J.* ; Matthews, J.* ; Border, R.* ; LaBianca, S.* ; Calle, X.* ; Meijsen, J.J.* ; Ingason, A.* ; Buil, A.* ; Vilhjálmsson, B.J.* ; Flint, J.* ; Bacanu, S.A.* ; Cai, N. ; Dahl, A.* ; Zaitlen, N.* ; Werge, T.* ; Kendler, K.S.* ; Schork, A.J.*

Genetic liability estimated from large-scale family data improves genetic prediction, risk score profiling, and gene mapping for major depression.

Am. J. Hum. Genet., DOI: 10.1016/j.ajhg.2024.09.009 (2024)
DOI PMC
Free by publisher: Verlagsversion online verfügbar 05/2025
Large biobank samples provide an opportunity to integrate broad phenotyping, familial records, and molecular genetics data to study complex traits and diseases. We introduce Pearson-Aitken Family Genetic Risk Scores (PA-FGRS), a method for estimating disease liability from patterns of diagnoses in extended, age-censored genealogical records. We then apply the method to study a paradigmatic complex disorder, major depressive disorder (MDD), using the iPSYCH2015 case-cohort study of 30,949 MDD cases, 39,655 random population controls, and more than 2 million relatives. We show that combining PA-FGRS liabilities estimated from family records with molecular genotypes of probands improves three lines of inquiry. Incorporating PA-FGRS liabilities improves classification of MDD over and above polygenic scores, identifies robust genetic contributions to clinical heterogeneity in MDD associated with comorbidity, recurrence, and severity and can improve the power of genome-wide association studies. Our method is flexible and easy to use, and our study approaches are generalizable to other datasets and other complex traits and diseases.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Depression ; Family Genetic Risk Scores ; Genealogy ; Genetic Liability ; Genetic Risk Profiles ; Pedigree
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Zeitschrift American Journal of Human Genetics, The
Verlag Elsevier
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Pioneer Campus (HPC)