| 1. |
- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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| 2. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 5. |
- Walker, Anthony P., et al.
(författare)
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Integrating the evidence for a terrestrial carbon sink caused by increasing atmospheric CO2
- 2021
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Ingår i: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 229:5, s. 2413-2445
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric carbon dioxide concentration ([CO2]) is increasing, which increases leaf‐scale photosynthesis and intrinsic water‐use efficiency. These direct responses have the potential to increase plant growth, vegetation biomass, and soil organic matter; transferring carbon from the atmosphere into terrestrial ecosystems (a carbon sink). A substantial global terrestrial carbon sink would slow the rate of [CO2] increase and thus climate change. However, ecosystem CO2 responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a [CO2]‐driven terrestrial carbon sink can appear contradictory. Here we synthesize theory and broad, multidisciplinary evidence for the effects of increasing [CO2] (iCO2) on the global terrestrial carbon sink. Evidence suggests a substantial increase in global photosynthesis since pre‐industrial times. Established theory, supported by experiments, indicates that iCO2 is likely responsible for about half of the increase. Global carbon budgeting, atmospheric data, and forest inventories indicate a historical carbon sink, and these apparent iCO2 responses are high in comparison to experiments and predictions from theory. Plant mortality and soil carbon iCO2 responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO2, albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change.
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| 6. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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| 7. |
- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 8. |
- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 9. |
- Bahadoer, Renu R., et al.
(författare)
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The survival gap between young and older patients after surgical resection for colorectal cancer remains largely based on early mortality : A EURECCA comparison of four European countries
- 2022
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Ingår i: Journal of Geriatric Oncology. - : Elsevier. - 1879-4068 .- 1879-4076. ; 13:6, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- Background: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first postoperative year. Over the last few years, improvements - especially in perioperative care - have increased survival. The current research investigates whether a survival gap between younger and older patients with CRC still exists on a national level in four European countries.Methods: Population-based data from Belgium, the Netherlands, Norway, and Sweden were collected from patients that underwent surgical resection for primary stage I-III CRC between 2007 and 2016. Relative survival and conditional relative survival (CS), with the condition of surviving the first postoperative year, were calculated for colon and rectal cancer separately, stratified for country and age category (<65, 65–75, ≥75 years). In addition, relative excess risk of death (RER) was estimated, and one-year excess mortality was calculated.Results: Data of 206,024 patients were analyzed. In general, compared to patients <65 years, patients ≥75 years had a worse survival during the first year after surgery, which was most pronounced in Belgium (RER colon cancer 2.5 [95% confidence interval (CI) 2.3–2.8] and RER rectal cancer 2.6 [95% CI 2.3–2.9]). After surviving the first year, CS was mostly not statistically different between patients <65 years and patients ≥75 years with stage I-II, with the exception of stage II colon cancer in Belgium. However, CS remained worse in the largest part of the patients ≥75 years with stage III colon or rectal cancer (except for rectal cancer in Norway).Conclusions: Although differences exist between the countries, the survival gap between young and older patients is based mainly on early mortality and remains only for stage III disease after surviving the first year.
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| 10. |
- Büntgen, Ulf, et al.
(författare)
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Limited capacity of tree growth to mitigate the global greenhouse effect under predicted warming
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- It is generally accepted that animal heartbeat and lifespan are often inversely correlated, however, the relationship between productivity and longevity has not yet been described for trees growing under industrial and pre-industrial climates. Using 1768 annually resolved and absolutely dated ring width measurement series from living and dead conifers that grew in undisturbed, high-elevation sites in the Spanish Pyrenees and the Russian Altai over the past 2000 years, we test the hypothesis of grow fast-die young. We find maximum tree ages are significantly correlated with slow juvenile growth rates. We conclude, the interdependence between higher stem productivity, faster tree turnover, and shorter carbon residence time, reduces the capacity of forest ecosystems to store carbon under a climate warming-induced stimulation of tree growth at policy-relevant timescales.
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