| 4451. |
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| 4452. |
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| 4453. |
- Perry, John R. B., et al.
(författare)
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Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m(2)) compared to obese cases (BMI >= 30 Kg/m(2)). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m(2)) or 4,123 obese cases (BMI >= 30 kg/m(2)), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P = 8.4610 29, OR = 1.13 [95% CI 1.09-1.18]), and this association was stronger than that in obese cases (P = 0.04, OR = 1.03 [95% CI 1.00-1.06]). A variant in HMG20A-previously identified in South Asians but not Europeans-was associated with type 2 diabetes in obese cases (P = 1.3 x 10(-8), OR= 1.11 [95% CI 1.07-1.15]), although this association was not significantly stronger than that in lean cases (P = 0.02, OR = 1.09 [95% CI 1.02-1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P = 0.0002). In the lean analysis, we observed a weighted per-risk allele OR = 1.13 [95% CI 1.10-1.17], P = 3.2 x 10(-14). This was larger than the same model fitted in the obese analysis where the OR = 1.06 [95% CI 1.05-1.08], P = 2.2 x 10(-16). This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes.
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| 4454. |
- Petersen, Gloria M, et al.
(författare)
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A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 224-228
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.
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| 4455. |
- Petersén, Åsa, et al.
(författare)
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Orexin loss in Huntington's disease.
- 2005
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 14:1, s. 39-47
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. Mutant huntingtin forms intracellular aggregates and is associated with neuronal death in select brain regions. The most studied mouse model (R6/2) of HD replicates many features of the disease, but has been reported to exhibit only very little neuronal death. We describe for the first time a dramatic atrophy and loss of orexin neurons in the lateral hypothalamus of R6/2 mice. Importantly, we also found a significant atrophy and loss of orexin neurons in Huntington patients. Like animal models and patients with impaired orexin function, the R6/2 mice were narcoleptic. Both the number of orexin neurons in the lateral hypothalamus and the levels of orexin in the cerebrospinal fluid were reduced by 72% in end-stage R6/2 mice compared with wild-type littermates, suggesting that orexin could be used as a biomarker reflecting neurodegeneration. Our results show that the loss of orexin is a novel and potentially very important pathology in HD.
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| 4456. |
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| 4457. |
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| 4458. |
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| 4459. |
- Phung, Nga, et al.
(författare)
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Photoprotection in metal halide perovskites by ionic defect formation
- 2022
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Ingår i: Joule. - : Elsevier BV. - 2542-4351. ; 6:9, s. 2152-2174
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Tidskriftsartikel (refereegranskat)abstract
- Photostability is critical for long-term solar cell operation. While light-triggered defects are usually reported as evidence of material degradation, we reveal that the formation of certain defects in metal halide perovskites is crucial for protection against intense or prolonged light exposure. We identify an inherent self-regulating cycle of formation and recovery of ionic defects under light exposure that mitigates the overheating of the lattice due to hot carrier cooling, which allows exposure to several thousand suns without degrading. The excess energy instead dissipates by forming defects, which in turn alters the optoelectronic properties of the absorber, resulting in a temporary reduction of photon absorption. Defects gradually recover to restore the original optoelectronic properties of the absorber. Photoprotection is a key feature for the photostability in plants. Thus, finding a protection mechanism in metal halide perovskites similar to those in nature is encouraging for the development of long-term sustainable solar cells.
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| 4460. |
- Pi, X. H., et al.
(författare)
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Chlorophyll-a concentrations in 82 large alpine lakes on the Tibetan Plateau during 2003-2017: temporal-spatial variations and influencing factors
- 2021
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Ingår i: International Journal of Digital Earth. - : Informa UK Limited. - 1753-8947 .- 1753-8955. ; 14:6, s. 714-735
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Tidskriftsartikel (refereegranskat)abstract
- As essential parts of the unique ecosystem of Tibetan Plateau (TP), the sizes and associated physical properties of alpine lakes have long been investigated. However, little is known about one of the most critical biogeochemical properties, i.e. the Chlorophyll-a (Chl-a) concentrations. Here, for the first time, we presented a comprehensive investigation of the temporal-spatial variations in Chl-a in 82 lakes (>50 km(2)) across the entire TP region, based on MODIS observations in the period of 2003-2017. The results showed that the 82 lakes exhibited an average long-term mean Chl-a of 3.3 +/- 4.3 mg m(-3), with high Chl-a lakes concentrated in the eastern and southern inner TP basin and northeastern parts of the TP. An interannual trend analysis revealed that lakes exhibiting (significantly) decreasing Chl-a trends and (significantly) increasing Chl-a trends were comparable in numbers but differed in distribution patterns. A correlation analysis indicated that at least 70% of the interannual variability in Chl-a values of lakes was significantly correlated with one of the four environmental factors (wind speed, ice cover duration, lake water surface temperature and surface runoff) and lake size. In addition, glacier meltwater tended to reduce lake Chl-a while salinity levels showed minor influences.
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