Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Glo...
Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined;these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs;defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims;type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative r
Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 ca...
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Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory *** is known about the biology of back pain, a leading cause of disability. Here the authors report 30 new back pain loci, implicating genes involved in cartilage/bone biology, as well as neurological and inflammatory processes.
BACKGROUND:Structural brain differences in the thalamus and the cortex have been widely reported in schizophrenia (SCZ) relative to neurotypical controls (NC). Most prior studies examined the thalamus as a whole, sing...
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BACKGROUND:Structural brain differences in the thalamus and the cortex have been widely reported in schizophrenia (SCZ) relative to neurotypical controls (NC). Most prior studies examined the thalamus as a whole, single region-of-interest. Additionally, findings in individuals at familial high-risk for schizophrenia (FHR) remain inconclusive. Here, we investigated whether local and network-wide thalamic-related structural alterations vary as a function of familial risk for schizophrenia.
METHODS:Structural MRI scans were obtained from 5,197 participants (3,409 NC, 257 FHR, 1,531 SCZ) across 32 cross-sectional samples within the ENIGMA Consortium. Random-effects meta-analyses, and network analyses were conducted on (i) local thalamic alterations (volume estimates of seven thalamic subdivisions), and (ii) network-wide thalamic alterations (thickness and surface-related thalamo-cortical/cortico-cortical co-variation patterns) across groups (NC, FHR, SCZ).
RESULTS:Individuals with SCZ showed significantly lower gray matter volume estimates in the anterior, pulvinar, medial, posterior, and ventral thalamic subdivisions compared to NC (q<0.05). FHR did not differ from NC. At the network-wide level, thalamo-cortical co-variations discriminated FHR from NC (q<0.05), with FHR showing intermediate co-variation between SCZ and NC. Cortico-cortical co-variation patterns revealed that SCZ and FHR shared similarly disconnected clustering configurations, distinct from NC (q<0.05).
CONCLUSIONS:Results revealed lower thalamic volume estimates in SCZ but not in FHR, hence yielding no evidence of a familial risk trait, whereas thalamo-cortical and cortico-cortical co-variation estimates were associated with familial risk for SCZ These findings suggest that, once the thalamus is parsed into subdivisions, network-wide thalamo-cortical features may identify trait-dependent, neurobiological correlates of genetic risk for SCZ.
BACKGROUND:Copy number variants (CNVs) increase risk for neurodevelopmental conditions. The neurobiological mechanisms linking these high-risk genetic variants to clinical phenotypes are largely unknown. An important ...
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BACKGROUND:Copy number variants (CNVs) increase risk for neurodevelopmental conditions. The neurobiological mechanisms linking these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals carrying CNVs are associated with their degree of penetrance.
METHODS:We investigated if increased CNV-penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA-CNV consortium. In the main analyses, we included 9,268 individuals (aged 7 to 90 years, 54% females), from which we identified 398 carriers of 36 neurodevelopmental CNVs at 20 distinct loci. A secondary analysis was performed including additional neuroimaging data from the ENIGMA-22q consortium, including 274 carriers of the 22q11.2 deletion and 291 non-carriers. CNV-penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk to develop either schizophrenia or other developmental disorders (including developmental delay, autism spectrum disorder and congenital malformations).
RESULTS:For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume. For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus.
CONCLUSIONS:Our findings link global and regional cortical morphometric features with CNV-penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.
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