Adolescent depression is a heritable psychiatric condition with rising global prevalence and severe long-term outcomes, yet its biological underpinnings remain poorly understood. We conducted the first genome-wide association study of adolescent-onset depression, comprising 102,428 cases (diagnosis or clinical symptom thresholds) and 286,911 controls, including diverse ancestries. Cross-ancestry meta-analysis identified 52 independent variants across 17 loci; European-only analysis found 61 variants at 29 loci, with a SNP-based heritability of 9.8%. Comparative analyses revealed two genes unique to adolescent-onset versus lifetime depression, enriched in neuronal subtypes, and two genes as potential drug repurposing targets. Polygenic scores were associated with adolescent-onset depression across ancestries, persistent depression trajectories, more severe outcomes, as well as reduced cortical volume, surface area and white matter integrity. Genetic correlation and Mendelian randomisation analyses support shared genetic liability and causal links with early puberty and modifiable health and behavioural risk factors. These findings uncover novel genetic loci and refine biological pathways underlying adolescent-onset depression, revealing age-specific mechanisms and early intervention opportunities.

BACKGROUND:Irregular working hours are a risk factor for cardiovascular diseases (CVD). AIMS:We studied ethnic disparities in the association between irregular working hours and CVD, as well as the mediating stress-related pathways. METHODS:Logistic regression was used to study the cross-sectional association between (a history of) irregular working hours and prevalent CVD (self-reported myocardial infarction, dotter/bypass operation or stroke) in 18 284 participants (18-71 years) in a population of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin from the HELIUS study. We considered three mediator models adjusting for behavioural, physiological and psychosocial stress. We tested for interaction between irregular working hours and ethnicity and stratified the analysis by ethnicity. RESULTS:The prevalence of CVD was 18% (717 out of 4041) and 14% (1963 out of 14 243) in individuals with versus without irregular working hours. Working irregular hours was associated with prevalent CVD (OR 1.27, 95% CI 1.15-1.40) after adjusting for sociodemographic confounders. There was a significant interaction between ethnicity and irregular working hours on CVD. Strongest associations with prevalent CVD were found for South-Asian Surinamese (OR 1.47, 95% CI 1.18-1.82), African Surinamese (OR 1.29, 95% CI 1.06-1.57) and Moroccans (OR 1.43, 95% CI 1.11-1.84). There were considerable ethnic differences in the mediating stress-related pathways that associate irregular working hours with prevalent CVD. CONCLUSIONS:Working irregular hours is associated with an increased prevalence of CVD in a multi-ethnic population. We show ethnic disparities in the associations between irregular working hours and CVD, as well as in the stress-related pathways that mediate these associations.

Social behaviour is a heritable, context-dependent trait that changes across social settings and development, influencing wellbeing and mental health. We present the first genome-wide meta-regression study of social behaviour from infancy to early adulthood, leveraging 491,246 repeat measures of low prosocial behaviour and peer/social difficulties in European-ancestry cohorts (Neff=121,777, Nind=73,321). We modelled heterogeneity in genetic effects across social domains, informants, and ages (2–29 years), capturing social context through genomic influences. Six loci were identified, including variation within CADM2 ( p =2.51x10-[9][1]). The SNP-based heritability was modest (2–7%), and the genetic architecture of social behaviour multidimensional. Polygenic scores demonstrated predictability and accuracy in independent European-ancestry cohorts and, partially, in African-ancestry cohorts (Nind=16,305). Genetic correlations with later-life and mental health outcomes showed context-dependent patterns. Modelling predicted onsets of associations with social behaviour revealed distinct profiles, as observed for autism, ADHD, depression and schizophrenia, highlighting novel opportunities to genetically proxy developmental trajectories. ### Competing Interest Statement H.L. reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals and Evolan Pharma AB; all outside the submitted work. H.L. is editor-in-chief of JCPP Advances. J.A.R-Q. was on the speakers bureau and/or acted as a consultant for Biogen, Idorsia, Casen-Recordati, Janssen-Cilag, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, BMS, Medice, Rubio, Uriach, Technofarma and Raffo in the last 3 years. J.A.R-Q. also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Idorsia, Janssen-Cilag, Rubio, Takeda, Bial and Medice. The Department of Psychiatry, chaired by J.A.R-Q., received unrestricted educational and research support from the following companies in the last 3 years: Exeltis, Idorsia, Janssen-Cilag, Neuraxpharm, Oryzon, Roche, Probitas and Rubio. E.D.R. has served as a speaker for Shire Sweden AB, a Takeda Pharmaceutical Company, outside of this work. S.B. discloses that he has in the last 3 years acted as a consultant or lecturer for Medice, Takeda, and LinusBio. S.B. receives royalties for textbooks and diagnostic tools from Hogrefe, UTB, Ernst Reinhardt, Kohlhammer, and Liber. S.B. is a partner in NeuroSupportSolutions International AB. All other authors declare no conflict of interest. R2D2-MH, Horizon Europe, 101057385 R2D2-MH, UK Research and Innovation (UKRI), under the UK government’s Horizon Europe funding guarantee, 10039383 R2D2-MH, Swiss State Secretariat for Education, Research and Innovation (SERI), contract number: 22.00277 ZonMW, TOP 40–00812–98–11010 Horizon Europe Research and Innovation Programme, FAMILY, 101057529, HappyMums, 101057390 European Research Council, TEMPO, 101039672 Dutch Ministry of Education, Culture, and Science and the Netherlands Organisation for Scientific Research, 024.001.003, Consortium on Individual Development, NWO-VICI, NWO-ZonMW: 016.VICI.170.200 Horizon 2020 research and innovation program, Contract grant no. 633595, DynaHealth, LongITools, 874739, EarlyCause, 848158 China Scholarship Council, 201706990036 Max Planck Society Radboud University Donders RSF 2025 Ter Meulen Grant of the Royal Netherlands Academy of Arts and Sciences (KNAW) Strategic Research Council (SRC) established within the Academy of Finland, decision no. 352700 Instituto de Salud Carlos III, co-funded by the European Union Fund (Fondo Social Europeo Plus, FSE+), contract no. CP22/00026 Research Council of Norway (RCN), #274611, #336085, #274611, #274611, #288083, #336078 South-Eastern Norway Regional Health Authority (HSO), #2020022, #2018059, #2021045 MRC Integrative Epidemiology Unit, University of Bristol, Medical Research Council, University of Bristol, MC\_UU\_00032/1 European Union, 101045526, 818425 University of Oulu, Academy of Finland Profi6, decision number AF 336449 Research Council of Finland, STAGE [Grant N° 101137146], IHEN [Grant N° 101137317], OBELISK Grant [N° 101080465], OBCT [Grant N° 101080250], TRIGGER [Grant N° 101057739] Research Council of Finland, 356888 MRC Centre for Environment and Health, Medical Research Council, UK, MR/S019669/1 Simons Foundation, 724306 Sir Henry Wellcome Postdoctoral Fellowship, 213514/Z/18/Z Ministry of Science, Technology and Innovation, https://ror.org/012s3r374, State Research Agency grant RYC2022-038136-I, European Union FSE+, State Research Agency grant PID2022-143106OA-I00, European Union FEDER William H. Gates Sr. Fellowship from the Alzheimer’s Disease Data Initiative UK Medical Research Council, Grant Nos. MR/V012878/1 and previously MR/M021475/1 US National Institutes of Health, AG046938 European Research Council under the European Union's Seventh Framework Programme, FP7/2007-2013, grant agreement n° 602768 UK Research and Innovation, 10063472 EU-AIMS (European Autism Interventions) & AIMS-2-TRIALS, European Union FP7 & Horizon2020 Programmes, the European Federation of Pharmaceutical Industries and Associations (EFPIA), AUTISM SPEAKS, Autistica, SFARI,, Innovative Medicines Initiative Joint Undertaking Grant No. 115300 and 777394, Horizon2020 supported programme CANDY Grant No. 847818 [1]: #ref-9

Abstract Introduction Shift-work is a riskfactor for cardiovascular diseases (CVD). We studied the association between irregular working hours and CVD in a multi-ethnic population in the Netherlands, and compared this association between various ethnicities. Methods Logistic regression was used to study the cross-sectional association between (a history of) irregular working hours and prevalent CVD (self-reported myocardial infarction, dotter/bypass operation or stroke) in 18.746 participants (18–71 years) of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, or Moroccan origin from the Healthy Life in an Urban Setting (HELIUS)-Study. We adjusted for sex, age, occupational level, smoking, alcohol use, physical inactivity, obesity, hypertension, diabetes mellitus, and hyperlipidemia. To study ethnic differences, we tested for interaction between irregular working hours and ethnicity with Dutch as the reference-population, and stratified the analysis by ethnicity. Results The prevalence CVD was 17.8% (740 out of 4.159) and 13.9% (2.026 out of 14.587) in the population with and without irregular working hours, respectively. Working irregular hours was associated with CVD (adjusted odds-ratio(OR) 1.18, (95%-confidence interval(CI): 1.07-1.30). Stratified by ethnicity, strongest associations with CVD were found for South-Asian Surinamese (OR 1.39, 95%-CI: 1.11-1.74) and Moroccans (OR 1.38, 95%-CI: 1.07, 1.79). The OR for CVD between individuals with versus without irregular working hours among the South-Asian Surinamese was significantly different from the Dutch (p=0.04). Discussion and conclusion The present study demonstrates that working irregular hours is an independent risk factor for CVD in a multi-ethnic population. In particular, individuals from South-Asian Surinamese and Moroccans origin working irregular hours are at increased risk to have developed CVD.

BACKGROUND:Regional and country-specific cardiovascular risk algorithms have been developed to improve CVD risk prediction. But it is unclear whether migrants' country-of-residence or country-of-birth algorithms agree in stratifying the CVD risk of these populations. We evaluated the risk stratification by the different algorithms, by comparing migrant country-of-residence-specific scores to migrant country-of-birth-specific scores for ethnic minority populations in the Netherlands.METHOD:data from the HELIUS study was used in estimating the CVD risk scores for participants using five laboratory-based (Framingham, Globorisk, Pool Cohort Equation II, SCORE II, and WHO II) and three nonlaboratory-based (Framingham, Globorisk, and WHO II) risk scores with the risk chart for the Netherlands. For the Globorisk, WHO II, and SCORE II risk scores, we also computed the risk scores using risk charts specified for the migrant home country. Risk categorization was first done according to the specification of the risk algorithm and then simplified to low (green), moderate (yellow and orange), and high risk (red).RESULTS:we observed differences in risk categorization for different risk algorithms ranging from 0% (Globorisk) to 13% (Framingham) for the high-risk category, as well as differences in the country-of-residence- and country-of-birth-specific scores. Agreement between different scores ranged from none to moderate. We observed a moderate agreement between the Netherlands-specific SCORE II and the country-of-birth SCORE II for the Turkish and a nonagreement for the Dutch Moroccan population.CONCLUSION:disparities exist in the use of the country-of-residence-specific, as compared to the country-of-birth, risk algorithms among ethnic minorities living in the Netherlands. Hence, there is a need for further validation of country-of-residence- and country-of-birth-adjusted scores to ascertain appropriateness and reliability.

IntroductionThere is a pressing need for non-invasive, cost-effective tools for early detection of Alzheimer's disease (AD). MethodsUsing data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), Cox proportional models were conducted to develop a multimodal hazard score (MHS) combining age, a polygenic hazard score (PHS), brain atrophy, and memory to predict conversion from mild cognitive impairment (MCI) to dementia. Power calculations estimated required clinical trial sample sizes after hypothetical enrichment using the MHS. Cox regression determined predicted age of onset for AD pathology from the PHS. ResultsThe MHS predicted conversion from MCI to dementia (hazard ratio for 80th versus 20th percentile: 27.03). Models suggest that application of the MHS could reduce clinical trial sample sizes by 67%. The PHS alone predicted age of onset of amyloid and tau. DiscussionThe MHS may improve early detection of AD for use in memory clinics or for clinical trial enrichment. HIGHLIGHTSA multimodal hazard score (MHS) combined age, genetics, brain atrophy, and memory.The MHS predicted time to conversion from mild cognitive impairment to dementia.MHS reduced hypothetical Alzheimer's disease (AD) clinical trial sample sizes by 67%.A polygenic hazard score predicted age of onset of AD neuropathology.

Background: Polygenic hazard scores (PHS) estimate age-dependent genetic risk of late-onset Alzheimer’s disease (AD), but there is limited information about the performance of PHS on real-world data where the population of interest differs from the model development population and part of the model genotypes are missing or need to be imputed. Objective: The aim of this study was to estimate age-dependent risk of late-onset AD using polygenic predictors in Nordic populations. Methods: We used Desikan PHS model, based on Cox proportional hazards assumption, to obtain age-dependent hazard scores for AD from individual genotypes in the Norwegian DemGene cohort ( n = 2,772). We assessed the risk discrimination and calibration of Desikan model and extended it by adding new genotype markers (the Desikan Nordic model). Finally, we evaluated both Desikan and Desikan Nordic models in two independent Danish cohorts: The Copenhagen City Heart Study (CCHS) cohort ( n = 7,643) and The Copenhagen General Population Study (CGPS) cohort ( n = 10,886). Results: We showed a robust prediction efficiency of Desikan model in stratifying AD risk groups in Nordic populations, even when some of the model SNPs were missing or imputed. We attempted to improve Desikan PHS model by adding new SNPs to it, but we still achieved similar risk discrimination and calibration with the extended model. Conclusion: PHS modeling has the potential to guide the timing of treatment initiation based on individual risk profiles and can help enrich clinical trials with people at high risk to AD in Nordic populations.

Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study®. This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commonly used univariate GWAS methods applied to region of interest (ROI) data. Functional follow up including gene-based analyses implicated 10% of all protein-coding genes and pointed towards pathways involved in neurogenesis and cell differentiation. Power analysis indicated that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. The large boost in power obtained with the vertex-wise MOSTest together with pronounced replication rates and highlighted biologically meaningful pathways underscores the advantage of multivariate approaches in the context of highly distributed polygenic architecture of the human brain.

Background COVID-19 is characterized by strikingly large, mostly unexplained, interindividual variation in symptom severity: while some individuals remain nearly asymptomatic, others suffer from severe respiratory failure. Previous vaccinations for other pathogens, in particular tetanus, may partly explain this variation, possibly by readying the immune system. Methods We made use of data on COVID-19 testing from 103,049 participants of the UK Biobank (mean age 71.5 years, 54.2% female), coupled to immunization records of the last ten years. Using logistic regression, covarying for age, sex, respiratory disease diagnosis, and socioeconomic status, we tested whether individuals vaccinated for tetanus, diphtheria or pertussis, differed from individuals that had only received other vaccinations on 1) undergoing a COVID-19 test, 2) being diagnosed with COVID-19, and 3) whether they developed severe COVID-19 symptoms. Results We found that individuals with registered diphtheria or tetanus vaccinations are less likely to develop severe COVID-19 than people who had only received other vaccinations (diphtheria odds ratio (OR)=0.47, p-value=5.3*10 -5 ; tetanus OR=0.52, p-value=1.2*10 -4 ). Discussion These results indicate that a history of diphtheria or tetanus vaccinations is associated with less severe manifestations of COVID-19. These vaccinations may protect against severe COVID-19 symptoms by stimulating the immune system. We note the correlational nature of these results, yet the possibility that these vaccinations may influence the severity of COVID-19 warrants follow-up investigations.

Background: COVID-19 is characterized by strikingly large, mostly unexplained, interindividual variation in symptom severity. While some individuals remain nearly asymptomatic, others suffer from severe respiratory failure. It has been hypothesized that previous vaccinations for other pathogens, in particular tetanus, may provide protection against severe COVID-19. Methods: We made use of data on COVID-19 testing from 103,049 participants of the UK Biobank (mean age 71.5 years, 54.2% female), coupled to immunization records of the last ten years. Using logistic regression, covarying for age, sex, respiratory disease diagnosis, and socioeconomic status, we tested whether individuals vaccinated for tetanus, diphtheria or pertussis, differed from individuals that had only received other vaccinations on 1) undergoing a COVID-19 test, 2) the outcome of this test, and 3) whether they developed severe COVID-19. Results: We found that individuals with registered diphtheria or tetanus vaccinations were less likely to develop severe COVID-19 than people who had only received other vaccinations (diphtheria OR=0.46, p=3.6x10-4; tetanus OR=0.50, p=5.8x10-4). Discussion: These results indicate that a history of diphtheria or tetanus vaccinations is associated with less severe manifestations of COVID-19. These vaccinations may protect against severe COVID-19 symptoms by stimulating the immune system. We note the correlational nature of these results, yet the possibility that these vaccinations may influence the severity of COVID-19 warrants follow-up investigations.

DNA sequence reads contain information about the genomic variants located on a single chromosome. By extracting and extending this information using the overlaps between the reads, the haplotypes of an individual can be obtained. Using parent-offspring relationships in a population can considerably improve the quality of the haplotypes obtained from short reads, as pedigree information can be used to correct for spurious overlaps (due to sequencing errors) and insufficient overlaps (due to short read lengths, low genomic variation and shallow coverage). We developed a novel method, PopPoly, to estimate polyploid haplotypes in an F1-population from short sequence data by taking into consideration the transmission of the haplotypes from the parents to the offspring. In addition, this information is employed to improve genotype dosage estimation and to call missing genotypes in the population. Through simulations, we compare PopPoly to other haplotyping methods and show its better performance. We evaluate PopPoly by applying it to a tetraploid potato cross at nine genomic regions involved in tuber formation.

Aims: Many people with a long-standing spinal cord injury have an inactive lifestyle. Although exercise self-efficacy is considered a key determinant of engaging in exercise, the relationship between exercise self-efficacy and physical activity remains unclear. Therefore, this study examines the relationship between exercise self-efficacy and the amount of physical activity in persons with long-standing spinal cord injury. Methods: This cross-sectional study included 268 individuals (aged 28-65 years) with spinal cord injury >= 10 years and using a wheelchair. Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities. Exercise self-efficacy was assessed with the Spinal cord injury Exercise Self-Efficacy Scale. Univariate and multivariable regression analyses were performed to test for the association between exercise self-efficacy and physical activity, controlling for supposed confounders. Results: Univariate regression analysis revealed that exercise self-efficacy was significantly related to the level of daily physical activity (beta = 0.05; 95% CI 0.04-0.07; 15% explained variance; p < 0.001). In multivariable regression analysis exercise self-efficacy remained, explaining a significant additional amount of the variance (2%; p < 0.001) of physical activity. Conclusion: Exercise-self efficacy is a weak but independent explanatory factor of the level of physical activity among persons with long-standing spinal cord injury. Longitudinal trials are needed to study the impact of interventions targeting an increase of exercise self-efficacy on the amount of physical activity performed.

Knowledge of “haplotypes”, i.e. phased and ordered marker alleles on a chromosome, is essential to answer many questions in genetics and genomics. By generating short pieces of DNA sequence, high-throughput modern sequencing technologies make estimation of haplotypes possible for single individuals. In polyploids, however, haplotype estimation methods usually require deep coverage to achieve sufficient accuracy. This often renders sequencing-based approaches too costly to be applied to large populations needed in studies of Quantitative Trait Loci (QTL).We propose a novel haplotype estimation method for polyploids, TriPoly, that combines sequencing data with Mendelian inheritance rules to infer haplotypes in parent-offspring trios. Using realistic simulations of short- read sequencing data for potato (Solanum tuberosum) and banana (Musa acuminata) trios, we show that TriPoly yields more accurate progeny haplotypes at low coverages compared to the existing methods that work on single individuals.

Haplotypes are the units of inheritance in an organism, and many genetic analyses depend on their precise determination. Methods for haplotyping single individuals use the phasing information available in Next Generation sequencing reads, by matching overlapping sNPs while penalizing post hoc nucleotide corrections made. Haplotyping diploids is relatively easy, but the complexity of the problem increases drastically for polyploid genomes, which are found in both model organisms and in economically relevant plant and animal species. While a number of tools are available for haplotyping polyploids, the effects of the genomic makeup and the sequencing strategy followed on the accuracy of these methods have hitherto not been thoroughly evaluated. We developed the simulation pipeline haplosim to evaluate the performance of haplotype estimation algorithms for polyploids: HapCompass, HapTree and SDhaP, in settings varying in sequencing approach, ploidy levels and genomic diversity, using tetraploid potato as the model. Our results show that sequencing depth is the major determinant of haplotype estimation quality, that 1 kb PacBio CCS reads and Illumina reads with large insert-sizes are competitive, and that all methods fail to produce good haplotypes when ploidy levels increase. Comparing the three methods, HapTree produces the most accurate estimates, but also consumes the most resources. There is clearly room for improvement in polyploid haplotyping algorithms.

Individual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome‐wide approaches of aggressive behavior in children. We analyzed data from nine population‐based studies and assessed aggressive behavior using well‐validated parent‐reported questionnaires. This is the largest sample exploring children's aggressive behavior to date (N = 18,988), with measures in two developmental stages (N = 15,668 early childhood and N = 16,311 middle childhood/early adolescence). First, we estimated the additive genetic variance of children's aggressive behavior based on genome‐wide SNP information, using genome‐wide complex trait analysis (GCTA). Second, genetic associations within each study were assessed using a quasi‐Poisson regression approach, capturing the highly right‐skewed distribution of aggressive behavior. Third, we performed meta‐analyses of genome‐wide associations for both the total age‐mixed sample and the two developmental stages. Finally, we performed a gene‐based test using the summary statistics of the total sample. GCTA quantified variance tagged by common SNPs (10–54%). The meta‐analysis of the total sample identified one region in chromosome 2 (2p12) at near genome‐wide significance (top SNP rs11126630, P = 5.30 × 10−8). The separate meta‐analyses of the two developmental stages revealed suggestive evidence of association at the same locus. The gene‐based analysis indicated association of variation within AVPR1A with aggressive behavior. We conclude that common variants at 2p12 show suggestive evidence for association with childhood aggression. Replication of these initial findings is needed, and further studies should clarify its biological meaning. © 2015 Wiley Periodicals, Inc.

PURPOSE: To investigate beta-amyloid precursor protein (beta-APP), ubiquitin, and glial fibrillary acid protein (GFAP) immunostaining as a diagnostic tool to aid in the discrimination between abusive head trauma and nonabusive head trauma in postmortem ocular histopathologic investigation.DESIGN: Retrospective cross-sectional study.METHODS: Seventy-four eyes of 37 infants were studied for hemorrhage and immunohistochemical expression of beta-APP, ubiquitin, and GFAP in the retina and optic nerve. Infants were assigned to abusive head trauma or control groups, according to published criteria.RESULTS: In the abusive head trauma group, positive beta-APP and ubiquitin immunostaining of the retina was significantly more likely to be found than in the control group, odds ratio (OR) 11.4, confidence interval (CI) 2.9-44.3; P < .001 and OR 8.8, CI 2.2-34.5; P = .002, respectively. Positive correlations were found between retinal expression of beta-APP and ubiquitin immunostaining and retinal hemorrhage. Vitreal hemorrhages, orbital fat hemorrhages, and macular folds could only be identified in abusive head trauma cases. Retinal hemorrhages were significantly more severe, occupied a larger proportion of the retina, and involved more retinal layers in abusive head trauma compared to controls (OR 2.7, CI 1.7-4.4; P < .001).CONCLUSIONS: This study shows correlations between positive retinal beta-APP and ubiquitin immunostaining as a sign of axonal injury in abusive head trauma. Axonal injury is a useful pathologic feature that can be demonstrated in postmortem ocular investigation of deceased children using immunohistochemical staining for beta-APP and ubiquitin with a high OR for abusive head trauma when compared to controls. (C) 2015, by Elsevier Inc. All rights reserved.

Polyploid organisms possess more than two copies of their core genome and therefore contain k>2 haplotypes for each set of ordered genomic variants. Polyploidy occurs often within the plant kingdom, among others in important corps such as potato (k=4) and wheat (k=6). Current sequencing technologies enable us to read the DNA and detect genomic variants, but cannot distinguish between the copies of the genome, each inherited from one of the parents. To detect inheritance patterns in populations, it is necessary to know the haplotypes, as alleles that are in linkage over the same chromosome tend to be inherited together. In this work, we develop mathematical optimisation algorithms to indirectly estimate haplotypes by looking into overlaps between the sequence reads of an individual, as well as into the expected inheritance of the alleles in a population. These algorithm deal with sequencing errors and random variations in the counts of reads observed from each haplotype. These methods are therefore of high importance for studying the genetics of polyploid crops.