Polygenic Risk Score Analysis Revealed Shared Genetic Background in Attention Deficit Hyperactivity Disorder and Narcolepsy

Authors

Nagahide Takahashi, Nagoya University
Tomoko Nishimura, Hamamatsu University
Taeko Harada, Hamamatsu University
Akemi Okumura, Hamamatsu University
Damee Choi, Hamamatsu University
Toshiki Iwabuchi, Hamamatsu University
Hitoshi Kuwabara, Hamamatsu University
Shu Takagi, Hamamatsu University
Yoko Nomura, CUNY Queens CollegeFollow
Jeffrey H. Newcorn, Mount Sinai School of Medicine
Nori Takei, Hamamatsu University
Kenji J. Tsuchiya, Hamamatsu University

Document Type

Article

Publication Date

2020

Abstract

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n=876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g.,P-value threshold < 0.05,β[SE], 5.815 [1.774];P=0.002) and inattention domain(e.g.,P-value threshold < 0.05,β[SE], 5.734 [1.761];P=0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD.

Comments

Originally published as: Takahashi, Nagahide, Tomoko Nishimura,Taeko Harada, Akemi Okumura, Damee Choi,Toshiki Iwabuchi, Hitoshi Kuwabara, Shu Takagai, Yoko Nomura, Jeffrey. H. Newcorn, Nori Takei and Kenji J. Tsuchiya. "Polygenic Risk Score Analysis Revealed Shared Genetic Background in Attention Deficit Hyperactivity Disorder and Narcolepsy," Translational Psychiatry, vol. 10, 2020, article number 284, doi: https://doi.org/10.1038/s41398-020-00971-7

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