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- Anney, R. J. L., et al.
(författare)
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Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) < 1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P= 9 x10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental- related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
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- Weiner, D. J., et al.
(författare)
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Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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- Chauvin, G., et al.
(författare)
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Discovery of a warm, dusty giant planet around HIP 65426
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The SHINE program is a high-contrast near-infrared survey of 600 young, nearby stars aimed at searching for and characterizing new planetary systems using VLT/SPHERE's unprecedented high-contrast and high-angular-resolution imaging capabilities. It is also intended to place statistical constraints on the rate, mass and orbital distributions of the giant planet population at large orbits as a function of the stellar host mass and age to test planet-formation theories.Methods. We used the IRDIS dual-band imager and the IFS integral field spectrograph of SPHERE to acquire high-contrast coronagraphic differential near-infrared images and spectra of the young A2 star HIP 65426. It is a member of the similar to 17 Myr old Lower Centaurus-Crux association. Results. At a separation of 830 mas (92 au projected) from the star, we detect a faint red companion. Multi-epoch observations confirm that it shares common proper motion with HIP 65426. Spectro-photometric measurements extracted with IFS and IRDIS between 0.95 and 2.2 mu m indicate a warm, dusty atmosphere characteristic of young low-surface-gravity L5-L7 dwarfs. Hot-start evolutionary models predict a luminosity consistent with a 6-12 M-Jup, T-eff = 1300-1600K and R = 1.5 +/- 0.1 R-Jup giant planet. Finally, the comparison with Exo-REM and PHOENIX BT-Settl synthetic atmosphere models gives consistent effective temperatures but with slightly higher surface gravity solutions of log(g) = 4.0-5.0 with smaller radii (1.0-1.3 R-Jup).Conclusions. Given its physical and spectral properties, HIP 65426 b occupies a rather unique placement in terms of age, mass, and spectral-type among the currently known imaged planets. It represents a particularly interesting case to study the presence of clouds as a function of particle size, composition, and location in the atmosphere, to search for signatures of non-equilibrium chemistry, and finally to test the theory of planet formation and evolution.
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- Kooij, J. J. S., et al.
(författare)
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Updated European Consensus Statement on diagnosis and treatment of adult ADHD
- 2019
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Ingår i: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 56, s. 14-34
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAttention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.MethodsThe European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.ResultsBesides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?ConclusionsADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
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- Hu, H., et al.
(författare)
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X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:1, s. 133-148
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Tidskriftsartikel (refereegranskat)abstract
- X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.
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| 9. |
- Lagrange, A. -M., et al.
(författare)
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Post-conjunction detection of beta Pictoris b with VLT/SPHERE
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 621
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Tidskriftsartikel (refereegranskat)abstract
- Context. With an orbital distance comparable to that of Saturn in the solar system, beta Pictoris b is the closest (semi-major axis similar or equal to 9 au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to beta Pictoris have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters.Aims. We aimed at further constraining beta Pictoris b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit.Methods. We used SPHERE at the VLT to precisely monitor the orbital motion of beta beta Pictoris b since first light of the instrument in 2014.Results. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6 au) and prevented further detection. We redetected beta Pictoris b on the northeast side of the disk at a separation of 139 mas and a PA of 30 degrees in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of a = 9.0 +/- 0.5 au (1 sigma), it definitely excludes previously reported possible long orbital periods, and excludes beta Pictoris b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.
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- Boccaletti, A., et al.
(författare)
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Observations of fast-moving features in the debris disk of AU Mic on a three-year timescale : Confirmation and new discoveries
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 614
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Tidskriftsartikel (refereegranskat)abstract
- Context. The nearby and young M star AU Mic is surrounded by a debris disk in which we previously identified a series of large-scale arch-like structures that have never been seen before in any other debris disk and that move outward at high velocities. Aims. We initiated a monitoring program with the following objectives: (1) track the location of the structures and better constrain their projected speeds, (2) search for new features emerging closer in, and ultimately (3) understand the mechanism responsible for the motion and production of the disk features. Methods. AU Mic was observed at 11 different epochs between August 2014 and October 2017 with the IR camera and spectrograph of SPHERE. These high-contrast imaging data were processed with a variety of angular, spectral, and polarimetric differential imaging techniques to reveal the faintest structures in the disk. We measured the projected separations of the features in a systematic way for all epochs. We also applied the very same measurements to older observations from the Hubble Space Telescope (HST) with the visible cameras STIS and ACS. Results. The main outcomes of this work are (1) the recovery of the five southeastern broad arch-like structures we identified in our first study, and confirmation of their fast motion (projected speed in the range 4-12 km s(-1) ); (2) the confirmation that the very first structures observed in 2004 with ACS are indeed connected to those observed later with STIS and now SPHERE; (3) the discovery of two new very compact structures at the northwest side of the disk (at 0.40 '' and 0.55 '' in May 2015) that move to the southeast at low speed; and (4) the identification of a new arch-like structure that might be emerging at the southeast side at about 0.4 from the star (as of May 2016). Conclusions. Although the exquisite sensitivity of SPHERE allows one to follow the evolution not only of the projected separation, but also of the specific morphology of each individual feature, it remains difficult to distinguish between possible dynamical scenarios that may explain the observations. Understanding the exact origin of these features, the way they are generated, and their evolution over time is certainly a significant challenge in the context of planetary system formation around M stars.
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