Biology subjects

Larsson, H.

Publications and source records attributed to Larsson, H..

9 recordsLinked to original sources

bioRxiv2021

Genetic influences on brain activation and large-scale functional connectivity during nociceptive processing: a twin study

Nociceptive processing in the human brain is a signal that enables harm avoidance, with large interindividual variance. The relative contributions of genes and environment to the neural structures that support nociception have not been studied in twins previously. Here, we employed a classic twin-design to determine brain structures influenced by additive genetics. We found genetic influences on nociceptive processing in the midcingulate cortex, bilateral posterior insulae and thalamus. In addition to brain activations, we found genetic contributions to large-scale functional connectivity during nociceptive processing. We conclude that additive genetics influence specific aspects of nociceptive processing, which improves our understanding of human nociceptive processing.

neuroscience↗

bioRxiv2020

Mythical and observable trends in human sex ratio at birth

The human sex ratio at birth (SRB) is defined as the ratio between the number of newborn boys to the total number of newborns per time unit. It is, typically, slightly greater than [Formula] (more boys than girls) and fluctuates over time. In this study, we sought to "myth-check" previously reported associations (and test new hypotheses) using variants of mixed-effect regression analyses and time-series models on two very large electronic health record datasets, representing the populations in the United States and Sweden, respectively. Our results revealed that neither dataset supported models in which the SRB changed seasonally or in response to variations in ambient temperature, and that an increased level of a diverse array of pollutants were associated with lower SRBs. Moreover, we found that increased levels of industrial and agricultural activity, which served as proxies for water pollution, were also associated with lower SRBs.

physiology↗

bioRxiv2020

Mapping the genetic and environmental aetiology of autistic traits in Sweden and the UK

BackgroundAutistic traits are influenced by both genetic and environmental factors, and are known to vary geographically in prevalence. But to what extent does their aetiology also vary from place to place? MethodsWe applied a novel spatial approach to data on autistic traits from two large twin studies, the Child and Adolescent Twin Study in Sweden (CATSS; N=16,677, including 8,307 twin pairs) and the Twins Early Development Study in the UK (TEDS; N=11,594, including 5,796 twin pairs), to explore how the influence of nature and nurture on autistic traits varies from place to place. ResultsWe present maps of gene- and environment-by geography interactions in Sweden and the United Kingdom (UK), showing geographical variation in both genetic and environmental influences across the two countries. In Sweden genetic influences appear higher in the far south and in a band running across the centre of the country. Environmental influences appear greatest in the south and north, with reduced environmental influence across the central band. In the UK genetic influences appear greater in the south, particularly in more central southern areas and the southeast, the Midlands and the north of England. Environmental influences appear greatest in the south and east of the UK, with less influence in the north and the west. ConclusionsWe hope this systematic approach to identifying aetiological interactions will inspire research to examine a wider range of previously unknown environmental influences on the aetiology of autistic traits. By doing so, we will gain greater understanding of how these environments draw out or mask genetic predisposition and interact with other environmental influences in the development of autistic traits.

genetics↗

bioRxiv2019

The fast and the frugal: Divergent locomotory strategies drive limb lengthening in theropod dinosaurs

Limb length, cursoriality and speed have long been areas of significant interest in theropod paleobiology as locomotory capacity, especially running ability, is critical in not just in prey pursuit but also to avoid become prey oneself. One aspect that is traditionally overlooked is the impact of allometry on running ability and the limiting effect of large body size. Since several different non-avian theropod lineages have each independently evolved body sizes greater than any known terrestrial carnivorous mammal, ∼1000kg or more, the effect that such larger mass has on movement ability and energetics is an area with significant implications for Mesozoic paleoecology. Here using expansive datasets, incorporating several different metrics to estimate body size, limb length and running speed, to calculate the effects of allometry running We test both on traditional metrics used to evaluate cursoriality in non-avian theropods such as distal limb length, relative hindlimb length as well as comparing the energetic cost savings of relative hindlimb elongation between members of the Tyrannosauridae and more basal megacarnivores such as Allosauroids or Ceratosauridae. We find that once the limiting effects of body size increase is incorporated, no commonly used metric including the newly suggested distal limb index (Tibia + Metatarsus/ Femur length) shows a significant correlation to top speed. The data also shows a significant split between large and small bodied theropods in terms of maximizing running potential suggesting two distinct strategies for promoting limb elongation based on the organisms’ size. For small and medium sized theropods increased leg length seems to correlate with a desire to increase top speed while amongst larger taxa it corresponds more closely to energetic efficiency and reducing foraging costs. We also find, using 3D volumetric mass estimates, that the Tyrannosauridae show significant cost of transport savings compared to more basal clades, indicating reduced energy expenditures during foraging and likely reduced need for hunting forays. This suggests that amongst theropods while no one strategy dictated hindlimb evolution. Amongst smaller bodied taxa the competing pressures of being both a predator and a prey item dominant while larger ones, freed from predation pressure, seek to maximize foraging ability. We also discuss the implications both for interactions amongst specific clades and Mesozoic paleobiology and paleoecological reconstructions as a whole.View Full Text

paleontology↗

bioRxiv2019

Machine-Learning Prediction of Comorbid Substance Use Disorders in ADHD Youth Using Swedish Registry Data

BackgroundChildren with attention-deficit/hyperactivity disorder (ADHD) have a high risk for substance use disorders (SUDs). Early identification of at-risk youth would help allocate scarce resources for prevention programs.\n\nMethodsPsychiatric and somatic diagnoses, family history of these disorders, measures of socioeconomic distress and information about birth complications were obtained from the national registers in Sweden for 19,787 children with ADHD born between 1989-1993. We trained 1) cross-sectional machine learning models using data available by age 17 to predict SUD diagnosis between ages 18-19; and 2) a longitudinal model to predict new diagnoses at each age.\n\nResultsThe area under the receiver operating characteristic curve (AUC) was 0.73 and 0.71 for the random forest and multilayer perceptron cross-sectional models. A prior diagnosis of SUD was the most important predictor, accounting for 25% of correct predictions. However, after excluding this predictor, our model still significantly predicted the first-time diagnosis of SUD during age 18-19 with an AUC of 0.67. The average of the AUCs from longitudinal models predicting new diagnoses one, two, five and ten years in the future was 0.63.\n\nConclusionsSignificant predictions of at-risk co-morbid SUDs in individuals with ADHD can be achieved using population registry data, even many years prior to the first diagnosis. Longitudinal models can potentially monitor their risks over time. More work is needed to create prediction models based on electronic health records or linked population-registers that are sufficiently accurate for use in the clinic.

neuroscience↗

bioRxiv2017

Copy number variation and neurodevelopmental problems in females and males in the general population

ObjectiveNeurodevelopmental problems (NPs) are childhood phenotypes that are more common in males. Conversely, anxiety and depression (which are frequently comorbid with NPs) are more common in females. Rare copy number variants (CNVs) have been implicated in clinically-defined NPs. Here, we aimed to characterise the relationship between rare CNVs with NPs and anxiety/depression in a population sample of twin children. Additionally, we examined whether sex-specific CNV effects underlie the sex bias of these disorders.\n\nMethodWe analysed a sample of N=12,982 children, of whom 5.3% had narrowly-defined NPs (clinically-diagnosed), 20.9% had broadly-defined NPs (based on validated screening measures, but no diagnosis) and 3.0% had clinically-diagnosed anxiety or depression. Rare (<1% frequency) CNVs were categorised by size (medium: 100-500kb or large: >500kb), type (duplication or deletion) and putative relevance to NPs (affecting previously implicated loci or evolutionarily-constrained genes). We tested for associations between the different CNV categories with NPs and anxiety/depression, followed by examination of sex-specific effects.\n\nResultsMedium deletions (OR(CI)=1.18(1.05-1.33),p=0.0053) and large duplications (OR(CI)=1.45(1.19-1.75),p=0.00017) were associated with broadly-defined NPs. Large deletions (OR(CI)=1.85(1.14-3.01),p=0.013) were associated with narrowly-defined NPs. The effect sizes increased for large NP-relevant CNVs (broadly-defined: OR(CI)=1.60(1.06-2.42),p=0.025; narrowly-defined: OR(CI)=3.64(2.16-6.13),p=1.2E-6). No sex differences in CNV burden were found in individuals with NPs (p>0.05). In individuals diagnosed with anxiety or depression, females were more likely to have large CNVs (OR(CI)=3.75(1.45-9.68),p=0.0064).\n\nConclusionRare CNVs are significantly associated with both narrowly- and broadly-defined NPs in a general population sample of children. Our results also suggest that large, rare CNVs may show sex-specific phenotypic effects.

genetics↗

bioRxiv2017

Genetic evidence for shared risks across psychiatric disorders and related traits in a Swedish population twin sample

Psychiatric traits related to categorically-defined psychiatric disorders are heritable and present to varying degrees in the general population. In this study, we test the hypothesis that genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits. We combine a contemporary twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Questionnaires assessing traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TD), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania and psychotic experiences were administered to a large, Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. PRS for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRS for each disorder and related continuous traits was tested. We found mild to strong genetic correlations between psychiatric diagnoses and corresponding traits (ranging from .31-.69) in the twin analyses. There was also evidence of association between PRS for ASD, ADHD, TD, OCD, anxiety, MDD and schizophrenia with related population traits. These results indicate that genetic factors which predispose to psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population, for many psychiatric phenotypes. This finding supports the conceptualization of psychiatric disorders as the extreme ends of continuous traits.

genetics↗

bioRxiv2017

The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology

Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder, with common genetic risk variants implicated in the clinical diagnosis and symptoms of ADHD. However, given evidence of comorbidity and genetic overlap across neurodevelopmental and externalizing conditions, it remains unclear whether these genetic risk variants are ADHD-specific. The aim of this study was to evaluate the associations between ADHD genetic risks and related neurodevelopmental and externalizing conditions, and to quantify the extent to which any such associations can be attributed to a general genetic liability towards psychopathology. We derived ADHD polygenic risk scores (PRS) for 13,460 children aged 9 and 12 years from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. Associations between ADHD PRS, a latent general psychopathology factor, and six latent neurodevelopmental and externalizing factors were estimated using structural equation modelling. ADHD PRS were statistically significantly associated with elevated levels of inattention, hyperactivity/impulsivity, autistic traits, learning difficulties, oppositional-defiant, and conduct problems (standardized regression coefficients=0.07-0.12). Only the association with specific hyperactivity/impulsivity remained significant after accounting for a general psychopathology factor, on which all symptoms loaded positively (standardized mean loading=0.61, range=0.32-0.91). ADHD PRS simultaneously explained 1% (p-value<0.001) of the variance in the general psychopathology factor and 0.50% (p-value<0.001) in the specific hyperactivity/impulsivity factor. Our results suggest that common genetic risk variants associated with ADHD have largely general pleiotropic effects on neurodevelopmental and externalizing traits in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms.

genetics↗

bioRxiv2017

A genetic investigation of sex bias in the prevalence of attention deficit hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. We analyzed genome-wide common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish population-registry data (N=77,905 cases, N=1,874,637 population controls). We find strong genetic correlation for ADHD across sex and no mean difference in polygenic burden across sex. In contrast, siblings of female probands are at an increased risk of ADHD, compared to siblings of male probands. The results also suggest that females with ADHD are at especially high risk of comorbid developmental conditions. Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity. However, autosomal common variants largely do not explain the sex bias in ADHD prevalence.

genetics↗