| 1. |
|
|
| 2. |
- Okada, Yukinori, et al.
(författare)
-
Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
-
Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
|
|
| 3. |
- Behrens, Jane W., et al.
(författare)
-
Personality- and size-related metabolic performance in invasive round goby (Neogobius melanostomus)
- 2020
-
Ingår i: Physiology and Behavior. - : Elsevier. - 0031-9384 .- 1873-507X. ; 215, s. 1-6
-
Tidskriftsartikel (refereegranskat)abstract
- Differences between individuals in behavioral type (i.e. animal personality) are ecologically and evolutionarily important because they can have significant effects on fitness components such as growth and predation risk. In the present study we are used the invasive round goby (Neogobius melanostomus) from an established population in controlled experiments to examine the relationships among personality, metabolic performance, and growth rate (inferred as size-at-age). Boldness was measured as the time to return to normal behavior after a simulated predator attack, where fish with shorter freezing times were categorized as "bold" and fish with longer times were categorized as "shy." We show that bold fish have significantly higher standard metabolic rate (SMR) than their shy conspecifics, whereas there was no difference between personality types in their maximum metabolic rate (MMR) or aerobic scope (AS). Bold fish furthermore had a smaller size-at-age as compared to shy fish. Together this provides evidence of a metabolic underpinning of personality where the high-SMR bold fish require more resources to sustain basic life functions than their low-SMR shy conspecifics, indicating that bold round goby from established populations with high densities (and high competition for food) pay a price of reduced growth rate.
|
|
| 4. |
- Ericsson, Philip, et al.
(författare)
-
Personality-dependent inter- and intraspecific foraging competition in the invasive round goby, Neogobius melanostomus
- 2021
-
Ingår i: Journal of Fish Biology. - : Wiley-Blackwell. - 0022-1112 .- 1095-8649. ; 98:5, s. 1234-1241
-
Tidskriftsartikel (refereegranskat)abstract
- This study examines the impact of boldness on foraging competition of the highly invasive round goby Neogobius melanostomus Pallas 1815. Individual risk tolerance, or boldness, was measured as the time to resume movement after a simulated predation strike. Fish that resumed movement faster were categorized as "bold," fish that took more time to resume movement were categorized as "shy" and those that fell in between these two categories were determined to have "intermediate" boldness. Competitive impacts of boldness in N. melanostomus were determined in a laboratory foraging experiment in which interspecific (juvenile Atlantic cod Gadus morhua Linnaeus 1758) and intraspecific (intermediate N. melanostomus) individuals were exposed to either bold or shy N. melanostomus competitors. G. morhua consumed fewer prey when competing with bold N. melanostomus than when competing with shy N. melanostomus, whereas intermediately bold N. melanostomus foraging was not affected by competitor boldness. Bold and shy N. melanostomus consumed similar amounts of prey, and the number of interactions between paired fish did not vary depending on the personality of N. melanostomus individuals. Therefore, intraspecific foraging competition was not found to be personality dependent. This study provides evidence that individual differences in boldness can mediate competitive interactions in N. melanostomus; nonetheless, results also show that competition is also governed by other mechanisms that require further study.
|
|
| 5. |
- Kapoor, Pooja Middha, et al.
(författare)
-
Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
|
|
| 6. |
- Shu, Xiang, et al.
(författare)
-
Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
-
Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
|
|
| 7. |
- Alexander, Stephen P. H., et al.
(författare)
-
The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
-
Ingår i: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
-
Tidskriftsartikel (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
|
|
| 8. |
- Behrens, Jane W, et al.
(författare)
-
Correlations between hemoglobin type and temperature preference of juvenile Atlantic cod Gadus morhua
- 2012
-
Ingår i: Journal of Experimental Marine Biology and Ecology. - 0022-0981. ; 413, s. 71-77
-
Tidskriftsartikel (refereegranskat)abstract
- Atlantic cod (Gadus morhua L.) exhibits polymorphic hemoglobin variants with the HbI locus showing a strong North-South geographic cline in frequency distribution of three main types (1/1, 1/2 and 2/2). This may indicate selective advantages of the different HbI types under various temperature regimes. Despite this only one study has directly examined the temperature preference of the two homozygous types, HbI- 1/1 and HbI-2/2, whereas the preference of the heterozygote (HbI-1/2) has never previously been addressed. By exposing fish to a 4–19 °C temperature gradient in an annular preference chamber we recorded the preferred temperature of wild juvenile G. morhua of all three main Hbl types originating from an area where they co-exist. HbI-2/2 G. morhua preferred significantly cooler water (8.9±0.2 °C) compared to the HbI-1/1 group (11±0.6 °C), this difference, however, not being as distinct as previously reported. There was pronounced inter-individual variation in the temperature preference of the HbI-1/2 G. morhua ranging between 6.7 and 13.8 °C, and their overall preference (10.5±0.9 °C) did not differ significantly from either of the homozygous HbI types. Notably, the mean range of utilized temperature (temperature span between 1st and 3rd quartile) was very similar between all 3 Hbl types with 3.2–3.5 °C. Considering the complexity of a trait like temperature preference, there are clearly many other factors besides HbI type that influence the thermal biology of cod, and therefore we also investigated possible associations between genotype and temperature preference for 12 variable candidate gene single nucleotide polymorphisms (SNPs) a priori expected to be related to growth and reproduction. There were, however, no significant correlations between temperature preference and any of the candidate gene SNPs indicating that none of these polymorphisms strongly associates with thermal behavior. Considering however the high-throughput genotyping methods becoming increasingly accessible there is great potential for association studies involving many more genetic markers to identify additional genetic polymorphisms that are important for temperature preference in G. morhua. In conclusion, we support the notion of a ‘warm’ (HbI-2/2) and a ‘cold’ (HbI-1/1) Hb type, although we suggest the difference to be more subtle than previously reported. Furthermore HbI-1/2 G. morhua shows rather inconsistent thermoregulatory behavior. To obtain a more definitive picture of the extent to which thermal niches are realized under natural conditions field observations in areas where the 3 HbI types co-exist should be performed.
|
|
| 9. |
- Eero, Margit, et al.
(författare)
-
Food for Thought Eastern Baltic cod in distress : biological changes and challenges for stock assessment
- 2015
-
Ingår i: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 72:8, s. 2180-2186
-
Tidskriftsartikel (refereegranskat)abstract
- The eastern Baltic (EB) cod (Gadus morhua) stock was depleted and overexploited for decades until the mid-2000s, when fishing mortality rapidly declined and biomass started to increase, as shown by stock assessments. These positive developments were partly assigned to effective management measures, and the EB cod was considered one of the most successful stock recoveries in recent times. In contrast to this optimistic view, the analytical stock assessment failed in 2014, leaving the present stock status unclear. Deteriorated quality of some basic input data for stock assessment in combination with changes in environmental and ecological conditions has led to an unusual situation for cod in the Baltic Sea, which poses new challenges for stock assessment and management advice. A number of adverse developments such as low nutritional condition and disappearance of larger individuals indicate that the stock is in distress. In this study, we (i) summarize the knowledge of recent changes in cod biology and ecosystem conditions, (ii) describe the subsequent challenges for stock assessment, and (iii) highlight the key questions where answers are urgently needed to understand the present stock status and provide scientifically solid support for cod management in the Baltic Sea.
|
|
| 10. |
- Flink, Henrik, et al.
(författare)
-
Consequences of eye fluke infection on anti-predator behaviours in invasive round gobies in Kalmar Sound
- 2017
-
Ingår i: Parasitology Research. - : Springer. - 0932-0113 .- 1432-1955. ; 116:6, s. 1653-1663
-
Tidskriftsartikel (refereegranskat)abstract
- Larvae of the eye fluke, Diplostomum, emerge from snails and infect fish by penetrating skin or gills, then move to the lens where they may impair the vision of the fish. For the fluke to reproduce, a bird must eat the infected fish, and it has been suggested that they therefore actively manipulate the fish's behaviour to increase the risk of predation. We found that round gobies Neogobius melanostomus, a species that was recently introduced to the Kalmar Sound of the Baltic Sea, had an eye fluke prevalence of 90-100%. We investigated how the infection related to behavioural variation in round gobies. Our results showed that the more intense the parasite-induced cataract, the weaker the host's response was to simulated avian attack. The eye flukes did not impair other potentially important anti-predator behaviours, such as shelter use, boldness and the preference for shade. Our results are in accordance with the suggestion that parasites induce changes in host behaviour that will facilitate transfer to their final host.
|
|
