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J Affect Disord. 2019 Nov 23. pii: S0165-0327(19)32310-9. doi: 10.1016/j.jad.2019.11.109. [Epub ahead of print]

Predictive power of the ADHD GWAS 2019 polygenic risk scores in independent samples of bipolar patients with childhood ADHD.

Author information

1
Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. Electronic address: maria.serbanescu@googlemail.com.
2
Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, United Kingdom.
3
SUNY Downstate Medical Center, Brooklyn, NY, United States.
4
Stefan S Nicolau Institute of Virology, Bucharest, Romania.
5
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital, Bonn, Bonn, Germany; Centre for Human Genetics, University of Marburg, Marburg, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland.
6
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital, Bonn, Bonn, Germany.
7
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital, Bonn, Bonn, Germany; Department of Biomedicine, University of Basel, Basel, Switzerland.
8
Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, United Kingdom. Electronic address: a.mcquillin@ucl.ac.uk.

Abstract

BACKGROUND:

Although there is evidence of genetic correlation between bipolar disorder (BP) and ADHD, the extent of the shared genetic risk and whether childhood ADHD (cADHD) influences the characteristics of the adult BP remain unclear. Our objectives were: (i) to test the ability of polygenic risk scores (PRS) derived from the latest PGC ADHD-GWAS (Demontis et al., 2019) to predict the presence of cADHD in BP patients; (ii) to examine the hypothesis that BP preceded by cADHD is a BP subtype with particular clinical traits and (iii) partially shares its molecular basis with ADHD.

METHOD:

PRS derived from the ADHD-GWAS-2019 were tested in BP patients (N = 942) assessed for cADHD with the Wender Utah Rating Scale and in controls from Romania and UK (N = 1616).

RESULTS:

The ADHD-PRS differentiated BP cases with cADHD from controls. Proband sex and BP age-of-onset significantly influenced the discriminative power of the ADHD-PRS. The ADHD-PRS predicted the cADHD score only in males and in BP cases with early age-of-onset (≤21 years). Bipolar patients with cADHD had a younger age-of-onset of mania/depression than patients without cADHD. The ADHD-PRS predicted the BP-affection status in the comparison of early-onset BP cases with controls suggesting a partial molecular overlap between early-onset BP and ADHD.

LIMITATIONS:

Retrospective diagnosis of cADHD, small sample size.

CONCLUSIONS:

The PRS-analysis indicated an acceptable predictive ability of the ADHD-SNP-set 2019 in independent BP samples. The best prediction of both cADHD and BP-affection status was found in the early-onset BP cases. The results may have impact on the individual disease monitoring.

KEYWORDS:

ADHD SNP set 2019; Age-of-onset; Bipolar disorder; Polygenic risk scores; Prediction

PMID:
31791676
DOI:
10.1016/j.jad.2019.11.109

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