| 1. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 2. |
- Larsson, Christina R., et al.
(författare)
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Suboptimal behaviour and knowledge regarding overnight glycaemia in adults with type 1 diabetes is common
- 2018
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Ingår i: Internal medicine journal (Print). - : Wiley-Blackwell Publishing Inc.. - 1444-0903 .- 1445-5994. ; 48:9, s. 1080-1086
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn people with type 1 diabetes (T1D), nocturnal hypoglycaemia (NH) can be slept through and can cause seizures, arrhythmias and death. Hypoglycaemia avoidance can induce hyperglycaemia and ketosis. Patient behaviour impacts clinical outcomes and may be changed by education.AimTo develop and utilise a survey to evaluate patient self‐management of overnight glycaemia in adults with T1D.MethodsAdults with T1D attending two Australian tertiary referral diabetes clinics completed a survey about their diabetes self‐management and glycaemic control, including responses to hypothetical pre‐bed blood glucose (BG) levels (4–20 mmol/L). Statistical analyses included t‐tests, Chi square tests and ANOVA with significance considered at P < 0.05.ResultsThere were 205 participants (103 females), with a mean (SD) age of 41 (17) years, T1D duration of 20 (16) years, HbA1c of 7.8(1.4)%, (61.3(8.2) mmol/mol), 38% on insulin pump therapy (CSII) and 36% with impaired hypoglycaemia awareness (IHA). Mean (SD) number of BG tests/day was 5.4 (2.7). Patients set higher BG target levels at bedtime and overnight: 7.5(1.4) and 7.1(1.3) mmol/L, respectively, compared to daytime (6.9(1.0); P < 0.0001 and P = 0.002 respectively). Only 36% of participants reported treating nocturnal hypoglycaemia (NH) with the recommended refined, then complex, carbohydrate. Only 28% of patients made safe choices in all bedtime BG scenarios, with higher rates for CSII users, P = 0.0005. Further education was desired by 32% of respondents, with higher rates in those with (44%) versus without IHA (25%), P = 0.006.ConclusionsMany adults with T1D have suboptimal knowledge and behaviour regarding overnight BG self‐management. A survey, piloted herein, may facilitate the identification of patients who could benefit from further education.
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| 3. |
- Law, Philip J., et al.
(författare)
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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 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
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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| 4. |
- Stenegren, Marcus, 1986-
(författare)
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Environmental conditions governing the distributions of symbiotic and free-living diazotrophic cyanobacteria in two tropical open oceans
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Di-nitrogen (N2) fixation plays a crucial role in oceanic carbon and nitrogen cycles and is important for marine biogeochemistry on regional and global scales. N2-fixing (diazotrophs) cyanobacteria are considered to contribute the most to marine nitrogen fixation, and thereby fuel the surrounding phytoplankton communities with bioavailable ammonia. Distribution and activity of phytoplankton, including diazotrophs, are largely driven by environmental conditions and temperature is often considered the main influence. A greater understanding of the environmental conditions that govern the diazotrophs, is vital to accurate predictions and estimations for the marine nitrogen budget, as well as understanding their impact on the nitrogen and carbon cycles.Therefore, the primary aim of this thesis was to determine abundances and distribution patterns for various cyanobacterial diazotrophs in two different regions that in spite of their hydrological differences are prime regions for diazotrophy. Moreover, we attempted to identify the environmental conditions that govern cyanobacterial diazotrophs abundance.In the first study we observed a clear separation of the unicellular diazotroph UCYN-A from the other diazotrophs, including the other unicellular types (UCYN-B, UCYN-C) in the Western Tropical South Pacific. The main driver of the vertical distribution of diazotrophs was based on a temperature-depth gradient, which was similar to the findings of our meta-analysis which included 11 additional datasets. Using newly and previously designed primers and probe sets for the UCYN-A1 and A2 hosts, we also observed discrepancies in detection and abundance for the two UCYN-A symbiotic strains (A1 and A2) and their respective hosts, which is in contrast to the current understanding of a highly specific and obligate partnership. Lastly, cross-hybridization tests revealed that the qPCR assay targeting the UCYN-A2 strain also enumerated UCYN-A1, demonstrating the difficulty in quantifying closely related strains.In the second study we distinguished the environmental conditions favoring two closely related heterocystous cyanobacterial strains of Richelia intracellularis (het-1 and het-2) which associate with two different diatom hosts (Rhizosolenia and Hemiaulus, respectively) in the Western Tropical North Atlantic (WTNA). In general, the Amazon River (AR) plume heavily influenced het-1 and het-2 abundances; higher densities were quantified at stations with mesohaline sea surface salinities and maximum abundances were detected in the sub-surface, below the freshwater discharge. However, maximum abundances at oceanic sea surface salinity stations were observed nearer to the surface. A piecewise Structural Equation Model (SEM) was developed and identified turbidity as an important factor governing het-1 and het-2 abundance. In addition, het-1 and het-2 distribution pattern was influenced by dissolved inorganic phosphorus (DIP) concentration and salinity. Het-1 tended to penetrate deeper waters and was favored by increased salinity, while the opposite was true for het-2.The results of this thesis contribute to a better understanding of marine cyanobacterial diazotrophs’ ecological niches and will prove useful in future predictions and research on nitrogen fixation, and the role of cyanobacterial diazotrophs in marine biogeochemistry.
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