@article{0b3668c2e8e04f388862cab36329af8c,
title = "Polygenic Risk Score–Derived Subcortical Connectivity Mediates Attention-Deficit/Hyperactivity Disorder Diagnosis",
abstract = "Background: Attention-deficit/hyperactivity disorder (ADHD) has substantial heritability, and a recent large-scale investigation has identified common genome-wide significant loci associated with increased risk for ADHD. Along the same lines, many studies using noninvasive neuroimaging have identified differences in brain functional connectivity in children with ADHD. We attempted to bridge these studies to identify differences in functional connectivity associated with common genetic risk for ADHD using polygenic risk score (PRS). Methods: We computed ADHD PRSs for all participants in our sample (N = 315, children 7–13 years of age, 196 with ADHD and 119 unaffected comparison children) using ADHD data from the Psychiatric Genomics Consortium as a discovery set. Magnetic resonance imaging was used to evaluate resting-state functional connectivity of targeted subcortical structures. Results: The functional connectivity between 2 region pairs demonstrated a significant correlation to PRS: right caudate–parietal cortex and nucleus accumbens–occipital cortex. Connectivity between these areas, in addition to being correlated with PRS, was correlated with ADHD status. The connection between the caudate and the parietal region acted as a statistical suppressor, such that when it was included in a path model, the association between PRS and ADHD status was enhanced. Conclusions: Our results suggest that functional connectivity to certain subcortical brain regions is directly altered by genetic variants, and certain cortico–subcortical connections may modulate ADHD-related genetic effects.",
keywords = "ADHD, Caudate, Genetics, Nucleus accumbens, Polygenic risk score, Subcortical",
author = "Hermosillo, {Robert J.M.} and Mooney, {Michael A.} and Eric Fezcko and Eric Earl and Mollie Marr and Darrick Sturgeon and Anders Perrone and Dominguez, {Oscar Miranda} and Faraone, {Stephen V.} and Beth Wilmot and Nigg, {Joel T.} and Fair, {Damien A.}",
note = "Funding Information: This work was supported by the National Institutes of Health National Institute of Mental Health (Grant Nos. R01-MH099064 and R37-MH-59105 [to JTN], Grant No. MH086654 [to JTN and DAF], Grant Nos. MH096773 , MH091238 , and MH115357 [to DAF]) and National Library of Medicine (Grant No. T15LM007088 [to EF] ). Funding Information: This work was supported by the National Institutes of Health National Institute of Mental Health (Grant Nos. R01-MH099064 and R37-MH-59105 [to JTN], Grant No. MH086654 [to JTN and DAF], Grant Nos. MH096773, MH091238, and MH115357 [to DAF]) and National Library of Medicine (Grant No. T15LM007088 [to EF]). This project made use of Connectome DB and Connectome Workbench, developed under the auspices of the Human Connectome Project at Washington University in St. Louis and associated consortium institutions (http://www.humanconnectome.org/). In the past year, SVF received income, potential income, travel expenses, continuing education support, and/or research support from Tris Pharma, Otsuka, Arbor, Ironshore, Shire, Akili Interactive Labs, Enzymotec, Sunovion, Supernus, and Genomind. With his institution, he holds U.S. patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press (Straight Talk About Your Child's Mental Health), Oxford University Press (Schizophrenia: The Facts), and Elsevier (ADHD: Non-Pharmacologic Interventions, an issue of Child and Adolescent Psychiatric Clinics of North America). He is principal investigator of www.adhdinadults.com. DAF is a founder of Nous Imaging, Inc. Any potential conflict of interest has been reviewed and managed by Oregon Health & Science University. OMD, EE, DAF, and AP are co-inventors of the Oregon Health & Science University Technology #2198 (co-owned with Washington University in St. Louis), FIRMM: Framewise Integrated Real-time MRI Monitoring, exclusively licensed to Nous Imaging, Inc. and any related research. Any potential conflict of interest has been reviewed and managed by Oregon Health & Science University. The other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: {\textcopyright} 2019 Society of Biological Psychiatry",
year = "2020",
month = mar,
doi = "10.1016/j.bpsc.2019.11.014",
language = "English (US)",
volume = "5",
pages = "330--341",
journal = "Biological Psychiatry: Cognitive Neuroscience and Neuroimaging",
issn = "2451-9022",
publisher = "Elsevier Inc.",
number = "3",
}