111 research outputs found
Associations between oxytocin-related genes and autistic-like traits.
Oxytocin has repeatedly been shown to influence human behavior in social contexts; also, a relationship between oxytocin and the pathophysiology of autism spectrum disorder (ASD) has been suggested. In the present study, we investigated single-nucleotide polymorphisms (SNPs) in the oxytocin gene (OXT) and the genes for single-minded 1 (SIM1), aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) and cluster of differentiation 38 (CD38) in a population of 1771 children from the Child and Adolescent Twin Study in Sweden (CATSS). Statistical analyses were performed to investigate any association between SNPs and autistic-like traits (ALTs), measured through ASD scores in the Autism-Tics, ADHD and other Co-morbidities inventory. Firstly, we found a statistically significant association between the SIM1 SNP rs3734354 (Pro352Thr) and scores for language impairment (p = .0004), but due to low statistical power this should be interpreted cautiously. Furthermore, nominal associations were found between ASD scores and SNPs in OXT, ARNT2 and CD38. In summary, the present study lends support to the hypothesis that oxytocin and oxytocin neuron development may have an influence on the development of ALTs and suggests a new candidate gene in the search for the pathophysiology of ASD.The Swedish Research CouncilThe Swedish Research Council for Health, Working Life and WelfareThe Swedish Brain FoundationSvenska Sällskapet för Medicinsk Forskning (SSMF)Fredrik and Ingrid Thurings stiftelseÅke Wibergs stiftelseÅhlén-stiftelsenJeanssons-stiftelsenMagnus Bergvalls stiftelseSöderström-Königska stiftelsenMärta Lundqvists stiftelsethe Novo Nordisk FoundationAccepte
Association between ASMT and autistic-like traits in children from a Swedish nationwide cohort
Persons with autism spectrum disorders (ASDs) often display low levels of melatonin,
and it has been suggested that this decrease may be due to low activity of the
acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin
synthesis pathway. Moreover, genetic variants in ASMT have been associated with
autism, as well as with low ASMT activity and melatonin levels, suggesting that the low
ASMT activity observed in autism may partly be due to variation within the ASMT gene.
In this study, we present a symptom-based approach to investigate possible
associations between ASMT and autistic-like traits (ALTs) in the general population. To
this end, continuous measures of ALTs were assessed in a nationally representative
twin cohort (n=1771) from Sweden and six Single Nucleotide Polymorphisms (SNP)
and a duplication of exon 2 to 8 in ASMT were genotyped. Our results show a
nominally significant association, in girls, between one SNP (rs5949028) in the last
intron of ASMT and social interaction impairments. No significant association, however,
was observed with traits related to language impairment or restricted and repetitive
behavior. In conclusion, our results support the possible involvement of the ASMT
gene in ASDs and our finding that only one of three traits shows association suggests
that genetic research may benefit from taking a symptom-specific approach to identify
genes involved in autism psychopathology.VetenskapsrĂĄdetAccepte
Association study between autistic-like traits and polymorphisms in the autism candidate regions RELN, CNTNAP2, SHANK3, and CDH9/10
The Swedish Research CouncilThe Swedish Council for Working Life and Social ResearchThe Petrus and Augusta Hedlund FoundationĂ…ke Wiberg foundationĂ…hlens FoundationWilhelm and Martina Lundgren FoundationThe Sahlgrenska AcademyPublishe
Comparison of Two-Dimensional- and Three-Dimensional-Based U-Net Architectures for Brain Tissue Classification in One-Dimensional Brain CT
Brain tissue segmentation plays a crucial role in feature extraction, volumetric quantification, and morphometric analysis of brain scans. For the assessment of brain structure and integrity, CT is a non-invasive, cheaper, faster, and more widely available modality than MRI. However, the clinical application of CT is mostly limited to the visual assessment of brain integrity and exclusion of copathologies. We have previously developed two-dimensional (2D) deep learning-based segmentation networks that successfully classified brain tissue in head CT. Recently, deep learning-based MRI segmentation models successfully use patch-based three-dimensional (3D) segmentation networks. In this study, we aimed to develop patch-based 3D segmentation networks for CT brain tissue classification. Furthermore, we aimed to compare the performance of 2D- and 3D-based segmentation networks to perform brain tissue classification in anisotropic CT scans. For this purpose, we developed 2D and 3D U-Net-based deep learning models that were trained and validated on MR-derived segmentations from scans of 744 participants of the Gothenburg H70 Cohort with both CT and T1-weighted MRI scans acquired timely close to each other. Segmentation performance of both 2D and 3D models was evaluated on 234 unseen datasets using measures of distance, spatial similarity, and tissue volume. Single-task slice-wise processed 2D U-Nets performed better than multitask patch-based 3D U-Nets in CT brain tissue classification. These findings provide support to the use of 2D U-Nets to segment brain tissue in one-dimensional (1D) CT. This could increase the application of CT to detect brain abnormalities in clinical settings
Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration: The H70 Birth Cohort Study in Gothenburg
BACKGROUND AND OBJECTIVES: Studies associate chronic kidney disease (CKD) with neurodegeneration. This study investigated the relation between kidney function, blood, cerebrospinal fluid (CSF), and structural brain MRI markers of neurodegeneration, in a sample including individuals with and without CKD. METHODS: Participants from the Gothenburg H70 Birth Cohort Study, with data on plasma-neurofilament light (P-NfL), estimated glomerular filtration rate (eGFR) and structural brain MRI were included. Participants were invited to also have CSF collected. The primary endpoint of the present study was to determine any association between CKD and P-NfL. Secondary endpoints included cross-sectional associations between CKD, eGFR and cerebrospinal fluid (CSF)- and MRI-derived markers of neurodegeneration and Alzheimer's disease (AD) pathology (MRI: cortical thickness, hippocampal volume, lateral ventricle volume, white matter lesion volume; CSF: β-amyloid (Aβ) 42, Aβ42/40, Aβ42/p-tau, t-tau, p-tau, NfL). Participants with P-NfL and eGFR at baseline were re-examined on eGFR, 5.5 (5.3; 6.1) years (median; IQR) after the first visit, and the predictive value of P-NfL levels on incident CKD was estimated longitudinally, using a Cox proportional hazards model. RESULTS: We included 744 participants, 668 without CKD (Age 71 (70; 71) years, 50% males) and 76 with CKD (age 71 (70;71) years, 39% males). Biomarkers from cerebrospinal fluid (CSF) were analysed in 313 participants. 558 individuals returned for a re-examination of eGFR (75% response rate, age 76 (76; 77), 48% males, 76 new cases of CKD). Participants with CKD had higher P-NfL levels than those with normal kidney function (median; 18.8 versus 14.0 pg/mL, p<0.001), while MRI and CSF markers were similar between the groups. P-NfL was independently associated with CKD after adjustment for confounding variables, including hypertension and diabetes (OR; 3.231, p<0.001), in a logistic regression model. eGFR, and CSF Aβ 42/40: R=0.23, p=0.004 correlated in participants with Aβ42 pathology. P-NfL levels in the highest quartile were associated with incident CKD at follow-up (HR; 2.08 (1.14: 4.50)). DISCUSSION: In a community-based cohort of 70-year olds, P-NfL was associated with both prevalent and incident CKD, while CSF and/or imaging measures did not differ by CKD status. Participants with CKD and dementia presented similar levels of P-NfL
Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community-based sample of 70-year-olds.
Neurofilament light protein (NfL) in cerebrospinal fluid (CSF) and plasma (P) are suggested to be interchangeable markers of neurodegeneration. However, evidence is scarce from community-based samples. NfL was examined in a small-scale sample of 287 individuals from the Gothenburg H70 Birth cohort 1944 study, using linear models in relation to CSF and magnetic resonance imaging (MRI) biomarker evidence of neurodegeneration. CSF-NfL and P-NfL present distinct associations with biomarker evidence of Alzheimer's disease (AD) pathology and neurodegeneration. P-NfL was associated with several markers that are characteristic of AD, including smaller hippocampal volumes, amyloid beta (Aβ)42, Aβ42/40, and Aβ42/t-tau (total tau). CSF-NfL demonstrated associations with measures of synaptic and neurodegeneration, including t-tau, phosphorylated tau (p-tau), and neurogranin. Our findings suggest that P-NfL and CSF-NfL may exert different effects on markers of neurodegeneration in a small-scale community-based sample of 70-year-olds
Using magnetic resonance imaging to measure head muscles: An innovative method to opportunistically determine muscle mass and detect sarcopenia
Background
Sarcopenia is associated with multiple adverse outcomes. Traditional methods to determine low muscle mass for the diagnosis of sarcopenia are mainly based on dual-energy X-ray absorptiometry (DXA), whole-body magnetic resonance imaging (MRI) and bioelectrical impedance analysis. These tests are not always available and are rather time consuming and expensive. However, many brain and head diseases require a head MRI. In this study, we aim to provide a more accessible way to detect sarcopenia by comparing the traditional method of DXA lean mass estimation versus the tongue and masseter muscle mass assessed in a standard brain MRI.
Methods
The H70 study is a longitudinal study of older people living in Gothenburg, Sweden. In this cross-sectional analysis, from 1203 participants aged 70 years at baseline, we included 495 with clinical data and MRI images available. We used the appendicular lean soft tissue index (ALSTI) in DXA images as our reference measure of lean mass. Images from the masseter and tongue were analysed and segmented using 3D Slicer. For the statistical analysis, the Spearman correlation coefficient was used, and concordance was estimated with the Kappa coefficient.
Results
The final sample consisted of 495 participants, of which 52.3% were females. We found a significant correlation coefficient between both tongue (0.26) and masseter (0.33) with ALSTI (P < 0.001). The sarcopenia prevalence confirmed using the alternative muscle measure in MRI was calculated using the ALSTI (tongue = 2.0%, masseter = 2.2%, ALSTI = 2.4%). Concordance between sarcopenia with masseter and tongue versus sarcopenia with ALSTI as reference has a Kappa of 0.989 (P < 0.001) for masseter and a Kappa of 1 for the tongue muscle (P < 0.001). Comorbidities evaluated with the Cumulative Illness Rating Scale were significantly associated with all the muscle measurements: ALSTI (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.07–1.26, P < 0.001), masseter (OR 1.16, 95% CI 1.07–1.26, P < 0.001) and tongue (OR 1.13, 95% CI 1.04–1.22, P = 0.002); the higher the comorbidities, the higher the probability of having abnormal muscle mass.
Conclusions
ALSTI was significantly correlated with tongue and masseter muscle mass. When performing the sarcopenia diagnostic algorithm, the prevalence of sarcopenia calculated with head muscles did not differ from sarcopenia calculated using DXA, and almost all participants were correctly classified using both methods.publishedVersio
Slowing gait speed precedes cognitive decline by several years
INTRODUCTION: In this longitudinal study, we aimed to examine if slowing gait speed preceded cognitive decline and correlated with brain amyloidosis. METHODS: The sample (n = 287) was derived from the Gothenburg H70 Birth Cohort Studies, with follow-ups between 2000 and 2015. Gait speed was measured by indoor walk, and cognition using the Clinical Dementia Rating (CDR) score. All participants had CDR = 0 at baseline. Some participants had data on cerebrospinal fluid (CSF) amyloid beta (Aβ)1-42 concentrations at the 2009 examination. RESULTS: Gait speed for participants who worsened in CDR score during follow-up was slower at most examinations. Baseline gait speed could significantly predict CDR change from baseline to follow-up. Subjects with pathological CSF Aβ1- 42 concentrations at the 2009 visit had lost more gait speed compared to previous examinations. DISCUSSION: Our results indicate that gait speed decline precedes cognitive decline, is linked to Alzheimer's pathology, and might be used for early detection of increased risk for dementia development
Heritability and confirmation of genetic association studies for childhood asthma in twins.
BACKGROUND: Although the genetics of asthma has been extensively studied using
both quantitative and molecular genetic analysis methods, both approaches lack
studies specific to the childhood phenotype and including other allergic
diseases. This study aimed to give specific estimates for the heritability of
childhood asthma and other allergic diseases, to attempt to replicate findings
from genomewide association studies (GWAS) for childhood asthma and to test the
same variants against other allergic diseases. METHODS: In a cohort of 25 306
Swedish twins aged 9 or 12 years, data on asthma were available from parental
interviews and population-based registers. The interviews also inquired about
wheeze, hay fever, eczema, and food allergy. Through structural equation
modeling, the heritability of all phenotypes was calculated. A subset of 10 075
twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from
previous GWAS; these were first tested for association with asthma and
significant findings also against the other allergic diseases. RESULTS: The
heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other
allergic diseases, the range was approximately 0.60-0.80. Associations for six
SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80,
95% CI 0.74-0.86, P = 1.5*10(-8) ; other significant associations all below P =
3.5*10(-4) ). Of these, only rs3771180 in IL1RL1 was associated with any other
allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6) ).
CONCLUSION: Asthma and allergic diseases of childhood are highly heritable, and
these high-risk genetic variants associated specifically with childhood asthma,
except for one SNP shared with hay fever.The Swedish Research CouncilThe Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM)The Stockholm County Council (ALF project)The Strategic Research Program in Epidemiology at Karolinska InstitutetThe Swedish Heart-Lung FoundationThe Swedish Asthma and Allergy Association’s Research FoundationManuscrip
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