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- Pervjakova, Natalia, et al.
(författare)
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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 31:19, s. 3377-3391
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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- Moon, S., et al.
(författare)
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Present-Day Stress Field Influences Bedrock Fracture Openness Deep Into the Subsurface
- 2020
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 47:23
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Tidskriftsartikel (refereegranskat)abstract
- Fracturing of bedrock promotes water-rock interactions and influences the formation of the life-sustaining layer of soil at Earth's surface. Models predict that present-day stress fields should influence bedrock fracture openness, but testing this prediction has proven difficult because comprehensive fracture data sets are rarely available. We model the three-dimensional present-day stress field beneath the deglaciated, low-relief landscape of Forsmark, Sweden. We account for ambient regional stresses, pore pressure, topography, sediment weight, and seawater loading. We then compare the modeled stresses to a data set of similar to 50,000 fractures reaching depths of 600 m at Forsmark. We show that modeled failure proxies correlate strongly with the fraction of observed open fractures to depths of similar to 500 m. This result implies that the present-day regional stress field, affected by surface conditions and pore pressure, influences fracture openness in bedrock hundreds of meters beneath the surface, thereby preparing the rock for further weathering. Plain Language Summary The "critical zone"-the life-sustaining part of the Earth that extends from the top of the tree canopy to the bottom of permeable bedrock-is essential for ecosystems and agriculture. The opening of bedrock fractures and onset of water-rock interaction are crucial to the formation of the critical zone. Within the bedrock, the intensities of horizontal regional forces and vertical gravitational forces typically increase with depth. These force intensities, or stresses, are modified by surface effects associated with topography, the weight of overlying seawater and sediment, and by groundwater pressure. However, the influence of these surface effects on fractures has been difficult to observe because comprehensive fracture data sets are rare. In this study, we examine whether, and to what depths, bedrock may fracture under the influence of stress associated with surficial conditions. We compare bedrock stress calculations with similar to 50,000 fractures from 18 cores reaching depths of 600 m at Forsmark, Sweden. We find that the present-day stress field influences the opening of fractures to depths of 500 m, contributing to the formation of the critical zone and the preparation of rock for weathering hundreds of meters beneath the surface, much deeper than previously thought.
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- Moon, Seulgi, et al.
(författare)
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Present-Day Stress Field Influences Bedrock Fracture Openness Deep Into the Subsurface
- 2020
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 47:23
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Tidskriftsartikel (refereegranskat)abstract
- Fracturing of bedrock promotes water-rock interactions and influences the formation of the life-sustaining layer of soil at Earth's surface. Models predict that present-day stress fields should influence bedrock fracture openness, but testing this prediction has proven difficult because comprehensive fracture data sets are rarely available. We model the three-dimensional present-day stress field beneath the deglaciated, low-relief landscape of Forsmark, Sweden. We account for ambient regional stresses, pore pressure, topography, sediment weight, and seawater loading. We then compare the modeled stresses to a data set of similar to 50,000 fractures reaching depths of 600 m at Forsmark. We show that modeled failure proxies correlate strongly with the fraction of observed open fractures to depths of similar to 500 m. This result implies that the present-day regional stress field, affected by surface conditions and pore pressure, influences fracture openness in bedrock hundreds of meters beneath the surface, thereby preparing the rock for further weathering. Plain Language Summary The "critical zone"-the life-sustaining part of the Earth that extends from the top of the tree canopy to the bottom of permeable bedrock-is essential for ecosystems and agriculture. The opening of bedrock fractures and onset of water-rock interaction are crucial to the formation of the critical zone. Within the bedrock, the intensities of horizontal regional forces and vertical gravitational forces typically increase with depth. These force intensities, or stresses, are modified by surface effects associated with topography, the weight of overlying seawater and sediment, and by groundwater pressure. However, the influence of these surface effects on fractures has been difficult to observe because comprehensive fracture data sets are rare. In this study, we examine whether, and to what depths, bedrock may fracture under the influence of stress associated with surficial conditions. We compare bedrock stress calculations with similar to 50,000 fractures from 18 cores reaching depths of 600 m at Forsmark, Sweden. We find that the present-day stress field influences the opening of fractures to depths of 500 m, contributing to the formation of the critical zone and the preparation of rock for weathering hundreds of meters beneath the surface, much deeper than previously thought.
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