Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults / Salahuddin MOHAMMAD in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 34p. Titre : Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults Type de document : Texte imprimé et/ou numérique Auteurs : Salahuddin MOHAMMAD, Auteur ; Mélissa GENTREAU, Auteur ; Manon DUBOL, Auteur ; Gull RUKH, Auteur ; Jessica MWINYI, Auteur ; Helgi B. SCHIÖTH, Auteur Article en page(s) : 34p. Langues : Anglais (eng) Mots-clés : Humans  Cerebellum/diagnostic imaging/pathology  Brain Stem/diagnostic imaging/pathology  Magnetic Resonance Imaging  Male  Female  Phenotype  Adult  Multifactorial Inheritance  Genetic Predisposition to Disease  Organ Size  Middle Aged  Autistic Disorder/genetics/diagnostic imaging  Genome-Wide Association Study  Autism Spectrum Disorder/genetics/diagnostic imaging  Gray Matter/diagnostic imaging/pathology  Case-Control Studies  Autism  Brain MRI  Brainstem  Cerebellum  Polygenic risk score Index. décimale : PER Périodiques Résumé : Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~?31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain. En ligne : https://dx.doi.org/10.1186/s13229-024-00611-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults [Texte imprimé et/ou numérique] / Salahuddin MOHAMMAD, Auteur ; Mélissa GENTREAU, Auteur ; Manon DUBOL, Auteur ; Gull RUKH, Auteur ; Jessica MWINYI, Auteur ; Helgi B. SCHIÖTH, Auteur . - 34p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 34p. Mots-clés : Humans  Cerebellum/diagnostic imaging/pathology  Brain Stem/diagnostic imaging/pathology  Magnetic Resonance Imaging  Male  Female  Phenotype  Adult  Multifactorial Inheritance  Genetic Predisposition to Disease  Organ Size  Middle Aged  Autistic Disorder/genetics/diagnostic imaging  Genome-Wide Association Study  Autism Spectrum Disorder/genetics/diagnostic imaging  Gray Matter/diagnostic imaging/pathology  Case-Control Studies  Autism  Brain MRI  Brainstem  Cerebellum  Polygenic risk score Index. décimale : PER Périodiques Résumé : Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~?31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain. En ligne : https://dx.doi.org/10.1186/s13229-024-00611-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels / Baiba SVALBE ; Gundega STELFA ; Solveiga GRINBERGA ; Liga ZVEJNIECE ; Helgi B. SCHIÖTH ; Maija DAMBROVA in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 29 p. Titre : Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels Type de document : Texte imprimé et/ou numérique Auteurs : Baiba SVALBE, Auteur ; Gundega STELFA, Auteur ; Solveiga GRINBERGA, Auteur ; Liga ZVEJNIECE, Auteur ; Helgi B. SCHIÖTH, Auteur ; Maija DAMBROVA, Auteur Article en page(s) : 29 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice. En ligne : http://dx.doi.org/10.1186/s13229-023-00560-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels [Texte imprimé et/ou numérique] / Baiba SVALBE, Auteur ; Gundega STELFA, Auteur ; Solveiga GRINBERGA, Auteur ; Liga ZVEJNIECE, Auteur ; Helgi B. SCHIÖTH, Auteur ; Maija DAMBROVA, Auteur . - 29 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 29 p. Index. décimale : PER Périodiques Résumé : Deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice. En ligne : http://dx.doi.org/10.1186/s13229-023-00560-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Well-being spectrum traits are associated with polygenic scores for autism / Salahuddin MOHAMMAD in Autism Research, 16-10 (October 2023)  

Public ISBD [article]  inAutism Research > 16-10 (October 2023) . - p.1891-1902 Titre : Well-being spectrum traits are associated with polygenic scores for autism Type de document : Texte imprimé et/ou numérique Auteurs : Salahuddin MOHAMMAD, Auteur ; Markus J. T. DE RUIJTER, Auteur ; Gull RUKH, Auteur ; Mathias RASK-ANDERSEN, Auteur ; Jessica MWINYI, Auteur ; Helgi B. SCHIÖTH, Auteur Article en page(s) : p.1891-1902 Index. décimale : PER Périodiques Résumé : Abstract Individuals with autism spectrum disorder (ASD) tend to experience lower well-being as demonstrated mostly for children and adolescents in epidemiological studies. A further investigation of inclusive well-being, in terms of five well-being spectrum (5-WBS) traits including neuroticism, depression, loneliness, life satisfaction, and positive affect, among adults with ASD may deepen our understanding of their well-being, and lead to the possibility to further modify societal supportive mechanisms for individuals with ASD. This study aims to investigate if a genetic predisposition for ASD is associated with 5-WBS traits using polygenic risk score (PRS) analysis. PRS for ASD were calculated based on the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and were created in the independent cohort UK Biobank. Regression analyses were performed to investigate the association between ASD PRS and 5-WBS traits in the UK Biobank population including 337,423 individuals. ASD PRS were significantly associated with all 5-WBS traits, showing a positive association with the negative WBS traits, neuroticism (max R2?=?0.04%, p? En ligne : https://doi.org/10.1002/aur.3011 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Well-being spectrum traits are associated with polygenic scores for autism [Texte imprimé et/ou numérique] / Salahuddin MOHAMMAD, Auteur ; Markus J. T. DE RUIJTER, Auteur ; Gull RUKH, Auteur ; Mathias RASK-ANDERSEN, Auteur ; Jessica MWINYI, Auteur ; Helgi B. SCHIÖTH, Auteur . - p.1891-1902. in Autism Research > 16-10 (October 2023) . - p.1891-1902 Index. décimale : PER Périodiques Résumé : Abstract Individuals with autism spectrum disorder (ASD) tend to experience lower well-being as demonstrated mostly for children and adolescents in epidemiological studies. A further investigation of inclusive well-being, in terms of five well-being spectrum (5-WBS) traits including neuroticism, depression, loneliness, life satisfaction, and positive affect, among adults with ASD may deepen our understanding of their well-being, and lead to the possibility to further modify societal supportive mechanisms for individuals with ASD. This study aims to investigate if a genetic predisposition for ASD is associated with 5-WBS traits using polygenic risk score (PRS) analysis. PRS for ASD were calculated based on the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and were created in the independent cohort UK Biobank. Regression analyses were performed to investigate the association between ASD PRS and 5-WBS traits in the UK Biobank population including 337,423 individuals. ASD PRS were significantly associated with all 5-WBS traits, showing a positive association with the negative WBS traits, neuroticism (max R2?=?0.04%, p? En ligne : https://doi.org/10.1002/aur.3011 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

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