X- vs. Y-chromosome influences on human behavior: a deep phenotypic comparison of psychopathology in XXY and XYY syndromes.
Journal
Journal of neurodevelopmental disorders
ISSN: 1866-1955
Titre abrégé: J Neurodev Disord
Pays: England
ID NLM: 101483832
Informations de publication
Date de publication:
03 Oct 2024
03 Oct 2024
Historique:
received:
23
10
2023
accepted:
22
09
2024
medline:
4
10
2024
pubmed:
4
10
2024
entrez:
3
10
2024
Statut:
epublish
Résumé
Do different genetic disorders impart different psychiatric risk profiles? This question has major implications for biological and translational aspects of psychiatry, but has been difficult to tackle given limited access to shared batteries of fine-grained clinical data across genetic disorders. Using a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs)-Klinefelter (XXY/KS) and XYY syndrome (n = 102 and 64 vs. n = 74 and 60 matched XY controls, total n = 300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X- vs. Y-chromosome effects, and potential relevance for normative sex differences. We show that XXY/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY/KS which is strongly correlated with that of XYY (r = .75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS/XXY for most traits except mood/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY/KS on social problems. XXY/KS and XYY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ. This work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X- and Y-chromosome on human behavior.
Sections du résumé
BACKGROUND
BACKGROUND
Do different genetic disorders impart different psychiatric risk profiles? This question has major implications for biological and translational aspects of psychiatry, but has been difficult to tackle given limited access to shared batteries of fine-grained clinical data across genetic disorders.
METHODS
METHODS
Using a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs)-Klinefelter (XXY/KS) and XYY syndrome (n = 102 and 64 vs. n = 74 and 60 matched XY controls, total n = 300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X- vs. Y-chromosome effects, and potential relevance for normative sex differences.
RESULTS
RESULTS
We show that XXY/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY/KS which is strongly correlated with that of XYY (r = .75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS/XXY for most traits except mood/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY/KS on social problems. XXY/KS and XYY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ.
CONCLUSIONS
CONCLUSIONS
This work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X- and Y-chromosome on human behavior.
Identifiants
pubmed: 39363182
doi: 10.1186/s11689-024-09574-5
pii: 10.1186/s11689-024-09574-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
56Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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