Increased Fluctuating Asymmetry in a Naturally Occurring Hybrid Zone between the Stick Insects Bacillus Rossius Rossius and Bacillus Rossius Redtenbacheri

The impact of interracial hybridization on fluctuating asymmetry (FA) and phenotypic variability (σ2p) in a presumed natural hybrid zone between the stick insects, Bacillus rossius rossius Rossi and Bacillus rossius redtenbacheri Nasceti & Bullini (Phasmatodea: Bacillidea), found on the Italian island Sardinia was investigated. The lengths of three bilateral traits and three unilateral traits were measured, and each individual was genotyped by five microsatellite loci. The genotypic data clearly confirmed the existence of the hybrid zone on Sardinia. A significantly increased FA was found in the hybrids when compared to both parental subspecies, which this study attributes to genetic incompatibilities in the hybrids. The increase in FA was not correlated with any increase in σ2P in the hybrids, which indicates that in this case σ2p and FA originate from separate processes

Genome-wide analyses suggest parallel selection for universal traits may eclipse local environmental selection in a highly mobile carnivore

Ecological and environmental heterogeneity can produce genetic differentiation in highly mobile species. Accordingly, local adaptation may be expected across comparatively short distances in the presence of marked environmental gradients. Within the European continent, wolves (Canis lupus) exhibit distinct north-south population differentiation. We investigated more than 67-K single nucleotide polymorphism (SNP) loci for signatures of local adaptation in 59 unrelated wolves from four previously identified population clusters (northcentral Europe n=32, Carpathian Mountains n=7, Dinaric-Balkan n=9, Ukrainian Steppe n=11). Our analyses combined identification of outlier loci with findings from genome-wide association study of individual genomic profiles and 12 environmental variables. We identified 353 candidate SNP loci. We examined the SNP position and neighboring megabase (1Mb, one million bases) regions in the dog (C. lupus familiaris) genome for genes potentially under selection, including homologue genes in other vertebrates. These regions included functional genes for, for example, temperature regulation that may indicate local adaptation and genes controlling for functions universally important for wolves, including olfaction, hearing, vision, and cognitive functions. We also observed strong outliers not associated with any of the investigated variables, which could suggest selective pressures associated with other unmeasured environmental variables and/or demographic factors. These patterns are further supported by the examination of spatial distributions of the SNPs associated with universally important traits, which typically show marked differences in allele frequencies among population clusters. Accordingly, parallel selection for features important to all wolves may eclipse local environmental selection and implies long-term separation among population clusters.201

The effect of developmental temperature fluctuation on wing traits and stressed locomotor performance in Drosophila melanogaster, and its dependence on heterozygosity

Background: Natural environments fluctuate and all organisms experience some degree of environmental variance. Global climate models predict increasing environmental variance in the future. Yet we do not fully understand how environmental variation affects performance traits. Questions: Does temperature fluctuation during development affect adult size and wing shape in Drosophila melanogaster? If so, are the effects predictable? Do they depend on heterozygosity? Do fluctuations in developmental temperature affect adult physiological performance at high temperature? Methods: We tested the effect of one fluctuating (21 degrees C/29 degrees C) and several constant (21 degrees C, 23 degrees C, 25 degrees C, 27 degrees C, 29 degrees C) developmental temperature regimes on three wing morphometric traits (wing length, wing width, and wing shape) in an experiment using three inbred lines of D. melanogaster and their first-generation hybrids. We also tested the effect of fluctuating and constant developmental temperature on adult locomotor performance at several high and stressful test temperatures (32 degrees C, 34 degrees C, 36 degrees C, 38 degrees C, 40 degrees C). Results: Performance mostly declined if the flies were reared under the fluctuating temperature regime versus the constant temperature regime with the same mean (25 degrees C). Heterozygosity level also affected the traits investigated, with crossbreds usually having higher trait values. Crossbred genotypes compared across constant temperatures also showed greater plasticity in wing aspect. Conclusion: The widespread use of constant developmental temperatures in laboratory experiments may lead to overestimation of performance.Danish Council for Independent Research \ Natural Sciences [11-107166]; Danish Natural Science Research Council [11-103926, 09-065999, 95095995]; Carlsberg Foundation [2011-01-0059

North-south differentiation and a region of high diversity in European wolves (Canis lupus)

European wolves (Canis lupus) show population genetic structure in the absence of geographic barriers, and across relatively short distances for this highly mobile species. Additional information on the location of and divergence between population clusters is required, particularly because wolves are currently recolonizing parts of Europe. We evaluated genetic structure in 177 wolves from 11 countries using over 67K single nucleotide polymorphism (SNP) loci. The results supported previous findings of an isolated Italian population with lower genetic diversity than that observed across other areas of Europe. Wolves from the remaining countries were primarily structured in a north-south axis, with Croatia, Bulgaria, and Greece (Dinaric-Balkan) differentiated from northcentral wolves that included individuals from Finland, Latvia, Belarus, Poland and Russia. Carpathian Mountain wolves in central Europe had genotypes intermediate between those identified in northcentral Europe and the Dinaric-Balkan cluster. Overall, individual genotypes from northcentral Europe suggested high levels of admixture. We observed high diversity within Belarus, with wolves from western and northern Belarus representing the two most differentiated groups within northcentral Europe. Our results support the presence of at least three major clusters (Italy, Carpathians, Dinaric-Balkan) in southern and central Europe. Individuals from Croatia also appeared differentiated from wolves in Greece and Bulgaria. Expansion from glacial refugia, adaptation to local environments, and human-related factors such as landscape fragmentation and frequent killing of wolves in some areas may have contributed to the observed patterns. Our findings can help inform conservation management of these apex predators and the ecosystems of which they are part

Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior

Genetic architecture of ADHD and overlap with other psychiatric disorders and cognition-related phenotypes

Trastorno por déficit de atención e hiperactividad; Comorbilidad; Genética de trastornos cruzadosTrastorn per dèficit d'atenció i hiperactivitat; Comorbiditat; Genètica de trastorns creuatsAttention-deficit/hyperactivity disorder; Comorbidity; Cross-disorder geneticsAttention-deficit/hyperactivity disorder (ADHD) co-occurs with many other psychiatric disorders and traits. In this review, we summarize and interpret the existing literature on the genetic architecture of these comorbidities based on hypothesis-generating approaches. Quantitative genetic studies indicate that genetic factors play a substantial role in the observed co-occurrence of ADHD with many different disorders and traits. Molecular genetic correlations derived from genome-wide association studies and results of studies based on polygenic risk scores confirm the general pattern but provide effect estimates that are smaller than those from twin studies. The identification of the specific genetic variants and biological pathways underlying co-occurrence using genome-wide approaches is still in its infancy. The first analyses of causal inference using genetic data support causal relationships between ADHD and comorbid disorders, although bidirectional effects identified in some instances point to complex relationships. While several issues in the methodology and inferences from the results are still to be overcome, this review shows that the co-occurrence of ADHD with many psychiatric disorders and traits is genetically interpretable.This research has received funding from the EU’s Horizon 2020 research and innovation program under grant agreements no. 667302 (CoCA), 728018 (Eat2beNICE) and 2020604 (TIMESPAN) and from the ECNP Network ‘ADHD across the Lifespan' (https://www.ecnp.eu/researchinnovation/ECNP-networks/List-ECNP-Networks/). B Cormand has also been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (PID2021-1277760B-I100), the Ministerio de Sanidad, Servicios Sociales e Igualdad/Plan Nacional Sobre Drogas (PNSD-2017I050), Fundació La Marató de TV3 (202218-31), Generalitat de Catalunya/AGAUR (2021-SGR-1093), ICREA Academia 2021 and the European Union H2020 Programme (H2020/2014-2020) under grant agreements no. 841899 (GRASAD) and 101028810 (ATTENTIVE). M Ribasés was also supported by the European Union H2020 Programme (H2020/2014–2020) under grant agreement no. 848228 (DISCOvERIE), by the Instituto de Salud Carlos III (PI20/00041, CP09/00119 and CPII15/00023), by the Pla estratègic de recerca i innovació en salut (PERIS), Generalitat de Catalunya (METAL-Cat; SLT006/17/287), by the Agència de Gestió d'Ajuts Universitaris i de Recerca AGAUR, Generalitat de Catalunya (2017SGR1461) and by Fundació La Marató de TV3 (202228-30, 202228-31). JA Ramos-Quiroga was also supported by the European Union H2020 Programme (H2020/2014–2020) under grant agreement no. 848228 (DISCOvERIE). M Mitjans was supported by Horizon 2020 Marie Sklodowska-Curie Individual Fellowship from the European Commission under grant agreement no. 841899 (GRASAD), the MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU”/PRTR” (RYC2021-033573-I), Ministerio de Ciencia e Innovación (PID2022-139740OA-100) and the Agència de Gestió d'Ajuts Universitaris i de Recerca AGAUR, Generalitat de Catalunya (2021-SGR-1093). M Soler Artigas was supported by the Instituto de Salud Carlos III (P19/01224, PI22/00464 and CP22/00128) and by the European Regional Development Fund. B Franke and A Reif were also supported by funding from the EU’s Horizon 2020 research and innovation program under grant agreement no. 847879 (PRIME). B Franke also received relevant funding from the Netherlands Organization for Scientific Research (NWO) for the GUTS project (grant 024.005.011). D Demontis is supported by the Novo Nordisk Foundation (NNF20OC0065561 and NNF21SA0072102), the Lundbeck Foundation (R344-2020-1060), the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 965381 (TIMESPAN). AD Børglum was supported by the Lundbeck Foundation (R102-A9118, R155-2014-1724, and R248-2017-2003). Research reported in this publication was also supported by the National Institute of Mental Health of the National Institutes of Health under Award Number R01MH124851. The content of the publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or any of the other funding organisations mentioned here

Mortality in individuals with disruptive behavior disorders diagnosed by specialist services – A nationwide cohort study

Disruptive behavior disorders (DBDs), inclusive of oppositional defiant disorder (ODD) and conduct disorder (CD), are associated with outcomes likely to increase risk of mortality. Using Danish National Registers, a total of 1.92 million individuals including 9495 individuals with DBDs diagnosed by specialist services were followed from their first birthday to 2013. Those with and without DBDs were compared using mortality rate ratios (MRRs) estimated using Poisson regression and adjusted for calendar period, age, sex, family history of psychiatric disorders, maternal age at time of birth, paternal age at time of birth, parental education status, and parental employment status. Over the course of follow up, which totalled 24.9 million person-years, 5580 cohort members died including 78 individuals with DBDs. The mortality rate per 10,000 person-years was 9.66 for individuals with DBDs compared to 2.22 for those with no diagnosis. This corresponded to a fully adjusted MRR of 2.57 (95% confidence interval 2.04–3.20). Comorbid substance use disorder and attention-deficit/hyperactivity disorder resulted in the highest MRR across all categories. These findings demonstrate the excess mortality associated with DBDs.</p

Is there evidence of a causal link between childhood maltreatment and attention deficit/hyperactivity disorder? A systematic review of prospective longitudinal studies using the Bradford-Hill criteria

Background: Studies report an elevated risk of maltreatment in children with attention deficit/hyperactivity disorder (ADHD), and elevated levels of ADHD in people who suffered childhood maltreatment (CM). However, the direction(s) of causality between CM and ADHD remain unclear—does ADHD create a context for CM, does CM cause ADHD, or both? Objective: This study systematically reviews and qualitatively synthesizes the research evidence relating to this question using Bradford-Hill criteria for establishing causality—strength, temporality, dose-response and plausibility. Methods: We conducted a systematic review, following PRISMA guidelines, of prospective longitudinal studies examining both CM and ADHD. We then used Bradford-Hill criteria to assess the quality of evidence for a causal link between CM and ADHD. Results: All 11 included studies demonstrated an association between CM and ADHD. Seven included evidence for temporality: five suggesting that CM precedes ADHD in the lifespan; two suggesting ADHD precedes CM. Four studies demonstrated a dose response relationship in which greater CM exposure was associated with elevated risk of ADHD. Studies presented a range of plausible mechanisms, including CM causing ADHD through biological programming, versus ADHD causing CM through parental stress. Conclusions: The high quality prospective longitudinal studies reviewed confirm the association between ADHD and CM, but present conflicting evidence about the direction of causality and mechanisms underpinning this association. To better understand the complex interplay between CM and ADHD, more studies using new research designs will be required that can partition effects by type of CM and account for bidirectional effects and other complexities

Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy.

Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex co-occurring neurodevelopmental conditions. Their genetic architectures reveal striking similarities but also differences, including strong, discordant polygenic associations with educational attainment (EA). To study genetic mechanisms that present as ASD-related positive and ADHD-related negative genetic correlations with EA, we carry out multivariable regression analyses using genome-wide summary statistics (N = 10,610-766,345). Our results show that EA-related genetic variation is shared across ASD and ADHD architectures, involving identical marker alleles. However, the polygenic association profile with EA, across shared marker alleles, is discordant for ASD versus ADHD risk, indicating independent effects. At the single-variant level, our results suggest either biological pleiotropy or co-localisation of different risk variants, implicating MIR19A/19B microRNA mechanisms. At the polygenic level, they point to a polygenic form of pleiotropy that contributes to the detectable genome-wide correlation between ASD and ADHD and is consistent with effect cancellation across EA-related regions

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10 -6) and rs8057927 in CDH13 (P=1.39 × 10 -5). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10 -7). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10 -7). This signal was replicated in the follow-up analysis (P=2.3 × 10 -2). Significant interaction with maternal CMV infection was found for rs7902091 (P SNP × CMV =7.