| 1. |
- 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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| 2. |
- 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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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Szatmari, Peter, et al.
(författare)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 7. |
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| 8. |
- Akbarian, S, et al.
(författare)
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The PsychENCODE project
- 2015
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Ingår i: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 18:12, s. 1707-1712
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Tidskriftsartikel (refereegranskat)
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| 9. |
- State, S. P., et al.
(författare)
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Electrodeposited Sn-Cu-Ni alloys as lead-free solders on copper substrate using deep eutectic solvents : The influence of electrodeposition mode on the morphology, composition and corrosion behaviour
- 2024
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 477
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Tidskriftsartikel (refereegranskat)abstract
- In this work we present the pulsed current (PC) electrodeposition of Sn-Cu-Ni alloy as lead-free solder candidate, from choline chloride – ethylene glycol eutectic mixtures (1:2 molar ratio) onto copper metallic substrates. Electrolytes containing Sn2+, Cu2+ and Ni2+ salts in the selected deep eutectic solvent have been considered. The effect of the applied frequency of PC on the morphology, composition and melting point of the alloy is discussed and compared to the ones obtained using direct current (DC) plating mode. A refinement of the grain size and lower melting temperature of the alloy were noticed when pulsed current was applied. A comparative analysis of the electrochemical corrosion behaviour at macro- and micro- scale has been performed in 0.5 M and 0.1 M NaCl solutions involving potentiodynamic polarization curves, electrochemical impedance spectroscopy (EIS) and scanning vibrating electrode (SVET) techniques. Furthermore, an analysis after 96 h of exposure to salt mist test simulating a corrosive attack in harsh environment is presented, too. The obtained results showed enhanced corrosion resistance of the ternary alloys electrodeposited under PC conditions (the best for 1.67 Hz frequency) as compared to those using DC. Additionally, Raman spectroscopy evidenced the presence of tin oxi/hydroxy chloride and tin oxides as surface corrosion products. A corrosion mechanism has been proposed.
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| 10. |
- Wang, Sheng, et al.
(författare)
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De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis
- 2018
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Ingår i: Cell Reports. - : CELL PRESS. - 2211-1247. ; 24:13, s. 3441-
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Tidskriftsartikel (refereegranskat)abstract
- We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk.
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| 11. |
- Danielsson, B., et al.
(författare)
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Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective To study the occurrence of torsades de pointes (TdP) ventricular tachycardia in relation to use of drugs labelled with TdP risk, using two nationwide Swedish registers. Design Prospective register-based cohort study. Setting Entire Sweden. Participants Persons aged >= 18 years prescribed and dispensed any drug classified with TdP risk during 2006-2017, according to CredibleMeds. Persons with a registered TdP diagnosis during the study period, using drugs labelled with known (TdP 1), possible (TdP 2) or conditional (TdP 3) risk at the incident of TdP were examined. Primary outcome measures Occurrence of TdP in relation to exposure rates for individual drugs with TdP risk. Secondary outcome measures Concurrent use of more than one TdP-labelled drug in a person with a TdP diagnosis. Results During the study period, 410 TdP cases using drugs with TdP risk labels at the incident were registered; 205 women and 205 men, mean age 74.0 and 71.5 years, respectively. Antidepressants dominated (129/410, 30%), followed by antiarrhythmics (17%). Diuretics and gastric acid-secretion inhibitors, with TdP risk related to induction of hypokalaemia or hypomagnesaemia, were used in 56% and 32% of the 410 TdP cases, respectively. Among the most used antidepressants, citalopram with known TdP 1 risk was associated with both a higher absolute number and incidence of TdP per 100 000 users (two to four times), compared with mirtazapine with possible (TdP 2), and sertraline with conditional (TdP 3) risk. Multiple risk factors, including advanced age, cardiovascular disease and treatment with more than one TdP-classified drug, were frequently observed. Conclusions Antidepressants followed by antiarrhythmics dominated among TdP risk drugs used by adults with TdP diagnosis, the majority being >= 65 years. TdP risk class and concomitant medication should be considered when prescribing antidepressants to older patients.
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| 12. |
- Du, M., et al.
(författare)
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Improving real-time bidding using a constrained markov decision process
- 2017
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Ingår i: 13th International Conference on Advanced Data Mining and Applications, ADMA 2017. - Cham : Springer. - 9783319691787 ; , s. 711-726
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Konferensbidrag (refereegranskat)abstract
- Online advertising is increasingly switching to real-time bidding on advertisement inventory, in which the ad slots are sold through real-time auctions upon users visiting websites or using mobile apps. To compete with unknown bidders in such a highly stochastic environment, each bidder is required to estimate the value of each impression and to set a competitive bid price. Previous bidding algorithms have done so without considering the constraint of budget limits, which we address in this paper. We model the bidding process as a Constrained Markov Decision Process based reinforcement learning framework. Our model uses the predicted click-through-rate as the state, bid price as the action, and ad clicks as the reward. We propose a bidding function, which outperforms the state-of-the-art bidding functions in terms of the number of clicks when the budget limit is low. We further simulate different bidding functions competing in the same environment and report the performances of the bidding strategies when required to adapt to a dynamic environment.
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| 13. |
- Du, M., et al.
(författare)
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Time series modeling of market price in real-time bidding
- 2019
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Ingår i: ESANN 2019 - Proceedings, 27th European Symposium on Artificial Neural Networks, Computational Intelligence and Machine Learning. - : ESANN. ; , s. 643-648
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Konferensbidrag (refereegranskat)abstract
- Real-Time-Bidding (RTB) is one of the most popular online advertisement selling mechanisms. Modeling the highly dynamic bidding environment is crucial for making good bids. Market prices of auctions fluctuate heavily within short time spans. State-of-the-art methods neglect the temporal dependencies of bidders’ behaviors. In this paper, the bid requests are aggregated by time and the mean market price per aggregated segment is modeled as a time series. We show that the Long Short Term Memory (LSTM) neural network outperforms the state-of-the-art univariate time series models by capturing the nonlinear temporal dependencies in the market price. We further improve the predicting performance by adding a summary of exogenous features from bid requests.
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