Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder
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Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder. / 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.
In: Nature Genetics, Vol. 56, No. 2, 2024, p. 234-244.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder
AU - LaBianca, Sonja
AU - Brikell, Isabell
AU - Helenius, Dorte
AU - Loughnan, Robert
AU - Mefford, Joel
AU - Palmer, Clare E.
AU - Walker, Rebecca
AU - Gådin, Jesper R.
AU - Krebs, Morten
AU - Appadurai, Vivek
AU - Vaez, Morteza
AU - Agerbo, Esben
AU - Pedersen, Marianne Giørtz
AU - Børglum, Anders D.
AU - Hougaard, David M.
AU - Mors, Ole
AU - Nordentoft, Merete
AU - Mortensen, Preben Bo
AU - Kendler, Kenneth S.
AU - Jernigan, Terry L.
AU - Geschwind, Daniel H.
AU - Ingason, Andrés
AU - Dahl, Andrew W.
AU - Zaitlen, Noah
AU - Dalsgaard, Søren
AU - Werge, Thomas M.
AU - Schork, Andrew J.
N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature America, Inc. 2023.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1038/s41588-023-01593-7
DO - 10.1038/s41588-023-01593-7
M3 - Journal article
C2 - 38036780
AN - SCOPUS:85178235467
VL - 56
SP - 234
EP - 244
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -
ID: 383741206