학술논문
Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder
Document Type
Original Paper
Author
LaBianca, Sonja; Brikell, Isabell; Helenius, Dorte; Loughnan, Robert; Mefford, Joel; Palmer, Clare E.; Walker, Rebecca; Gådin, Jesper R.; Krebs, Morten; Appadurai, Vivek; Vaez, Morteza; Agerbo, Esben; Pedersen, Marianne Giørtz; Børglum, Anders D.; Hougaard, David M.; Mors, Ole; Nordentoft, Merete; Mortensen, Preben Bo; Kendler, Kenneth S.; Jernigan, Terry L.; Geschwind, Daniel H.; Ingason, Andrés; Dahl, Andrew W.; Zaitlen, Noah; Dalsgaard, Søren; Werge, Thomas M.; Schork, Andrew J.
Source
Nature Genetics. 56(2):234-244
Subject
Language
English
ISSN
1061-4036
1546-1718
1546-1718
Abstract
Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals. First, we identify one genome-wide significant locus by comparing cases with ADHD and autism spectrum disorder (ASD) to cases with ADHD but not ASD. Second, we show that cases with ASD and ADHD, substance use disorder and ADHD, or first diagnosed with ADHD in adulthood have unique polygenic score (PGS) profiles that distinguish them from complementary case subgroups and controls. Finally, a PGS for an ASD diagnosis in ADHD cases predicted cognitive performance in an independent developmental cohort. Our approach uncovered evidence of genetic heterogeneity in ADHD, helping us to understand its etiology and providing a model for studies of other disorders.
Genome-wide analyses yield insights into the polygenic effects contributing to clinical heterogeneity in attention deficit hyperactivity disorder, advancing understanding of its genetic etiology and serving as a model for future studies in other complex disorders.
Genome-wide analyses yield insights into the polygenic effects contributing to clinical heterogeneity in attention deficit hyperactivity disorder, advancing understanding of its genetic etiology and serving as a model for future studies in other complex disorders.