| 1. |
|
|
| 2. |
- Munn-Chernoff, M. A., et al.
(author)
-
Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
-
In: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
-
Journal article (peer-reviewed)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
|
|
| 3. |
- Silventoinen, K., et al.
(author)
-
The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
- 2019
-
In: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
-
Journal article (peer-reviewed)abstract
- The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Ip, H. F., et al.
(author)
-
Genetic association study of childhood aggression across raters, instruments, and age
- 2021
-
In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
-
Journal article (peer-reviewed)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Solmi, M, et al.
(author)
-
- 2022
-
In: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
-
Journal article (peer-reviewed)
|
|
| 13. |
|
|
| 14. |
- Jami, E. S., et al.
(author)
-
Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
-
In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
-
Journal article (peer-reviewed)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
|
|
| 15. |
- Maes, S.L., et al.
(author)
-
Environmental drivers of increased ecosystem respiration in a warming tundra
- 2024
-
In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 629:8010, s. 105-113
-
Journal article (peer-reviewed)abstract
- Arctic and alpine tundra ecosystems are large reservoirs of organic carbon. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain. This hampers the accuracy of global land carbon–climate feedback projections. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9–2.0 °C] in air and 0.4 °C [CI 0.2–0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22–38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.
|
|
| 16. |
- Silventoinen, K., et al.
(author)
-
Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region : An individual-based pooled analysis of 40 twin cohorts
- 2017
-
In: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 106:2, s. 457-466
-
Journal article (peer-reviewed)abstract
- Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood.Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity.Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs).Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI.Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.
|
|
| 17. |
|
|
| 18. |
- Jelenkovic, A., et al.
(author)
-
Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994
- 2016
-
In: eLIFE. - Cambridge, United Kingdom : eLife Sciences Publications. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.
|
|
| 19. |
- Anderson, Cynthia M., et al.
(author)
-
Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2009-31 January 2010
- 2010
-
In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:3, s. 576-579
-
Journal article (peer-reviewed)abstract
- This article documents the addition of 220 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Allanblackia floribunda, Amblyraja radiata, Bactrocera cucurbitae, Brachycaudus helichrysi, Calopogonium mucunoides, Dissodactylus primitivus, Elodea canadensis, Ephydatia fluviatilis, Galapaganus howdenae howdenae, Hoplostethus atlanticus, Ischnura elegans, Larimichthys polyactis, Opheodrys vernalis, Pelteobagrus fulvidraco, Phragmidium violaceum, Pistacia vera, and Thunnus thynnus. These loci were cross-tested on the following species: Allanblackia gabonensis, Allanblackia stanerana, Neoceratitis cyanescens, Dacus ciliatus, Dacus demmerezi, Bactrocera zonata, Ceratitis capitata, Ceratitis rosa, Ceratits catoirii, Dacus punctatifrons, Ephydatia mulleri, Spongilla lacustris, Geodia cydonium, Axinella sp., Ischnura graellsii, Ischnura ramburii, Ischnura pumilio, Pistacia integerrima and Pistacia terebinthus.
|
|
| 20. |
- Furberg, Helena, et al.
(author)
-
Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
-
Journal article (peer-reviewed)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Maier, O., et al.
(author)
-
ISLES 2015-A public evaluation benchmark for ischemic stroke lesion segmentation from multispectral MRI
- 2017
-
In: Medical Image Analysis. - : Elsevier BV. - 1361-8415 .- 1361-8423. ; 35, s. 250-269
-
Journal article (peer-reviewed)abstract
- Ischemic stroke is the most common cerebrovascular disease, and its diagnosis, treatment, and study relies on non-invasive imaging. Algorithms for stroke lesion segmentation from magnetic resonance imaging (MRI) volumes are intensely researched, but the reported results are largely incomparable due to different datasets and evaluation schemes. We approached this urgent problem of comparability with the Ischemic Stroke Lesion Segmentation (ISLES) challenge organized in conjunction with the MICCAI 2015 conference. In this paper we propose a common evaluation framework, describe the publicly available datasets, and present the results of the two sub-challenges: Sub-Acute Stroke Lesion Segmentation (SISS) and Stroke Perfusion Estimation (SPES). A total of 16 research groups participated with a wide range of state-of-the-art automatic segmentation algorithms. A thorough analysis of the obtained data enables a critical evaluation of the current state-of-the-art, recommendations for further developments, and the identification of remaining challenges. The segmentation of acute perfusion lesions addressed in SPES was found to be feasible. However, algorithms applied to sub-acute lesion segmentation in SISS still lack accuracy. Overall, no algorithmic characteristic of any method was found to perform superior to the others. Instead, the characteristics of stroke lesion appearances, their evolution, and the observed challenges should be studied in detail. The annotated ISLES image datasets continue to be publicly available through an online evaluation system to serve as an ongoing benchmarking resource (www.isles-challenge.org).
|
|
| 24. |
- Danilovich, T., et al.
(author)
-
ATOMIUM: halide molecules around the S-type AGB star W Aquilae
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
-
Journal article (peer-reviewed)abstract
- Context. S-type asymptotic giant branch (AGB) stars are thought to be intermediates in the evolution of oxygen- to carbon-rich AGB stars. The chemical compositions of their circumstellar envelopes are also intermediate but have not been studied in as much detail as their carbon- and oxygen-rich counterparts. W Aql is a nearby S-type star, with well-known circumstellar parameters, making it an ideal object for in-depth study of less common molecules. Aims. We aim to determine the abundances of AlCl and AlF from rotational lines, which have been observed for the first time towards an S-type AGB star. In combination with models based on PACS observations, we aim to update our chemical kinetics network based on these results. Methods. We analyse ALMA observations towards W Aql of AlCl in the ground and first two vibrationally excited states and AlF in the ground vibrational state. Using radiative transfer models, we determine the abundances and spatial abundance distributions of (AlCl)-Cl-35, (AlCl)-Cl-37, and AlF. We also model HCl and HF emission and compare these models to PACS spectra to constrain the abundances of these species. Results. AlCl is found in clumps very close to the star, with emission confined within 0 ''.1 of the star. AlF emission is more extended, with faint emission extending 0 ''.2 to 0 ''.6 from the continuum peak. We find peak abundances, relative to H-2, of 1.7 x 10(-7) for (AlCl)-Cl-35, 7 x 10(-8) for (AlCl)-Cl-37, and 1 x 10(-7) for AlF. From the PACS spectra, we find abundances of 9.7 x 10(-8) and <= 10(-8), relative to H-2, for HCl and HF, respectively. Conclusions. The AlF abundance exceeds the solar F abundance, indicating that fluorine synthesised in the AGB star has already been dredged up to the surface of the star and ejected into the circumstellar envelope. From our analysis of chemical reactions in the wind, we conclude that AlF may participate in the dust formation process, but we cannot fully explain the rapid depletion of AlCl seen in the wind.
|
|
| 25. |
- Wallström, Sofia, 1988, et al.
(author)
-
ATOMIUM: Molecular inventory of 17 oxygen-rich evolved stars observed with ALMA
- 2024
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 681
-
Journal article (peer-reviewed)abstract
- Context. The dusty winds of cool evolved stars are a major contributor of the newly synthesised material enriching the Galaxy and future generations of stars. However, the details of the physics and chemistry behind dust formation and wind launching have yet to be pinpointed. Recent spatially resolved observations show the importance of gaining a more comprehensive view of the circumstellar chemistry, but a comparative study of the intricate interplay between chemistry and physics is still difficult because observational details such as frequencies and angular resolutions are rarely comparable. Aims. Aiming to overcome these deficiencies, ATOMIUM is an ALMA Large Programme to study the physics and chemistry of the circumstellar envelopes of a diverse set of oxygen-rich evolved stars under homogeneous observing conditions at three angular resolutions between ∼0.02′1.4′. Here we summarize the molecular inventory of these sources, and the correlations between stellar parameters and molecular content. Methods. Seventeen oxygen-rich or S-Type asymptotic giant branch (AGB) and red supergiant (RSG) stars have been observed in several tunings with ALMA Band 6, targeting a range of molecules to probe the circumstellar envelope and especially the chemistry of dust formation close to the star. We systematically assigned the molecular carriers of the spectral lines and measured their spectroscopic parameters and the angular extent of the emission of each line from integrated intensity maps. Results. Across the ATOMIUM sample, we detect 291 transitions of 24 different molecules and their isotopologues. This includes several first detections in oxygen-rich AGB/RSG stars: PO v = 1, SO2 v1 = 1 and v2 = 2, and several high energy H2O transitions. We also find several first detections in S-Type AGB stars: vibrationally excited HCN v2 = 2,3 and SiS v = 4,5,6, as well as first detections of the molecules SiC, AlCl, and AlF in W Aql. Overall, we find strong correlations between the following molecular pairs: CS and SiS, CS and AlF, NaCl and KCl, AlO and SO, SO2 and SO, and SO2 and H2O; meaning both molecules tend to have more detected emission lines in the same sources. The measured isotopic ratios of Si and S are found to be consistent with previous measurements, except for an anomalously high 29Si/30Si ratio of 4 ± 1 in the RSG VX Sgr. Conclusions. This paper presents the overall molecular inventory and an initial analysis of the large ATOMIUM dataset, laying the groundwork for future work deriving molecular abundances and abundance profiles using radiative transfer modeling which will provide more rigorous tests for chemical models.
|
|
