TY - JOUR
T1 - No signs of neurodegenerative effects in 15q11.2 BP1-BP2 copy number variant carriers in the UK Biobank
AU - Boen, R.
AU - Kaufmann, T.
AU - Frei, O.
AU - van der Meer, D.
AU - Djurovic, S.
AU - Andreassen, O.A.
AU - Selmer, K.K.
AU - Alnaes, D.
AU - Sonderby, I.E.
N1 - Funding Information:
This research has been conducted using the UK Biobank Resource under Application Number 27412. We acknowledge the support from the Research Council of Norway #223273 (NORMENT) and #276082 (TK). IES is supported by South-Eastern Norway Regional Health Authority (#2020060) and Kristian Gerhard Jebsen Stiftelsen (SKGJ-MED-021). RB is supported by South-Eastern Norway Regional Health Authority (#2020060). This work has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement No 847776. This work was performed on Services for sensitive data (TSD), the University of Oslo, Norway, with resources provided by UNINETT Sigma2 - the National Infrastructure for High Performance Computing and Data Storage in Norway.
Funding Information:
This research has been conducted using the UK Biobank Resource under Application Number 27412. We acknowledge the support from the Research Council of Norway #223273 (NORMENT) and #276082 (TK). IES is supported by South-Eastern Norway Regional Health Authority (#2020060) and Kristian Gerhard Jebsen Stiftelsen (SKGJ-MED-021). RB is supported by South-Eastern Norway Regional Health Authority (#2020060). This work has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement No 847776. This work was performed on Services for sensitive data (TSD), the University of Oslo, Norway, with resources provided by UNINETT Sigma2 - the National Infrastructure for High Performance Computing and Data Storage in Norway.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/2/18
Y1 - 2023/2/18
N2 - The 15q11.2 BP1-BP2 copy number variant (CNV) is associated with altered brain morphology and risk for atypical development, including increased risk for schizophrenia and learning difficulties for the deletion. However, it is still unclear whether differences in brain morphology are associated with neurodevelopmental or neurodegenerative processes. This study derived morphological brain MRI measures in 15q11.2 BP1-BP2 deletion (n = 124) and duplication carriers (n = 142), and matched deletion-controls (n = 496) and duplication-controls (n = 568) from the UK Biobank study to investigate the association with brain morphology and estimates of brain ageing. Further, we examined the ageing trajectory of age-affected measures (i.e., cortical thickness, surface area, subcortical volume, reaction time, hand grip strength, lung function, and blood pressure) in 15q11.2 BP1-BP2 CNV carriers compared to non-carriers. In this ageing population, the results from the machine learning models showed that the estimated brain age gaps did not differ between the 15q11.2 BP1-BP2 CNV carriers and non-carriers, despite deletion carriers displaying thicker cortex and lower subcortical volume compared to the deletion-controls and duplication carriers, and lower surface area compared to the deletion-controls. Likewise, the 15q11.2 BP1-BP2 CNV carriers did not deviate from the ageing trajectory on any of the age-affected measures examined compared to non-carriers. Despite altered brain morphology in 15q11.2 BP1-BP2 CNV carriers, the results did not show any clear signs of apparent altered ageing in brain structure, nor in motor, lung or heart function. The results do not indicate neurodegenerative effects in 15q11.2 BP1-BP2 CNV carriers.
AB - The 15q11.2 BP1-BP2 copy number variant (CNV) is associated with altered brain morphology and risk for atypical development, including increased risk for schizophrenia and learning difficulties for the deletion. However, it is still unclear whether differences in brain morphology are associated with neurodevelopmental or neurodegenerative processes. This study derived morphological brain MRI measures in 15q11.2 BP1-BP2 deletion (n = 124) and duplication carriers (n = 142), and matched deletion-controls (n = 496) and duplication-controls (n = 568) from the UK Biobank study to investigate the association with brain morphology and estimates of brain ageing. Further, we examined the ageing trajectory of age-affected measures (i.e., cortical thickness, surface area, subcortical volume, reaction time, hand grip strength, lung function, and blood pressure) in 15q11.2 BP1-BP2 CNV carriers compared to non-carriers. In this ageing population, the results from the machine learning models showed that the estimated brain age gaps did not differ between the 15q11.2 BP1-BP2 CNV carriers and non-carriers, despite deletion carriers displaying thicker cortex and lower subcortical volume compared to the deletion-controls and duplication carriers, and lower surface area compared to the deletion-controls. Likewise, the 15q11.2 BP1-BP2 CNV carriers did not deviate from the ageing trajectory on any of the age-affected measures examined compared to non-carriers. Despite altered brain morphology in 15q11.2 BP1-BP2 CNV carriers, the results did not show any clear signs of apparent altered ageing in brain structure, nor in motor, lung or heart function. The results do not indicate neurodegenerative effects in 15q11.2 BP1-BP2 CNV carriers.
KW - LONGITUDINAL CHANGES
KW - CEREBRAL-CORTEX
KW - BRAIN
KW - AGE
KW - IDENTIFICATION
KW - BIOMARKER
KW - VOLUMES
KW - GENES
U2 - 10.1038/s41398-023-02358-w
DO - 10.1038/s41398-023-02358-w
M3 - Article
C2 - 36807331
SN - 2158-3188
VL - 13
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 61
ER -