| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- Ellinor, Patrick T., et al.
(författare)
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Meta-analysis identifies six new susceptibility loci for atrial fibrillation
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:6, s. 88-670
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
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| 3. |
- Granath, Gustaf
(författare)
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Peatland Bryophytes in a Changing Environment : Ecophysiological Traits and Ecosystem Function
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peatlands are peat forming ecosystems in which not fully decomposed plant material builds up the soil. The sequestration of carbon into peat is mainly associated with the bryophyte genus Sphagnum (peat mosses), which dominate and literally form most peatlands. The responses of Sphagnum to environmental change help us to understand peatland development and function and to predict future changes in a rapidly changing world. In this thesis, the overarching aim was to use ecophysiological traits to investigate mechanisms behind the response of Sphagnum to elevated N deposition, and, processes connected to ecosystem shift and ecosystem function of peatlands. Regarding elevated N deposition, three experiments were performed at different scales (country-wide to greenhouse). Independent of scale and species, apical tissue N concentration increased with increasing N input until N saturation was reached. Maximum photosynthetic rate, a trait evaluating photosynthetic capacity, increased with N input and could be well predicted by tissue N concentration. Thus, the physiological responses of Sphagnum to N deposition are often positive and I found no evidence of toxic effects. Production did, however, not increase with N input, and results of the N:P ratio suggested that P limitation, and possibly other elements, might hamper growth under high N input. The effect of P limitation was, in contrast to current view, most pronounced in fast growing species indicating species specific responses to nutrient imbalance. I explored the puzzling, but historically frequently occurring, rich fen to bog ecosystem shift; a shift from a species-rich ecosystem dominated by brown mosses, to a species-poor one with greater carbon storage that is Sphagnum-dominated. The bog-dwelling species of Sphagnum grew well, to our surprise, when in contact with rich fen water but was not a strong competitor compared to rich fen Sphagnum species. If submerged under rich fen water (high pH), the bog Sphagnum species died while rich fen species of Sphagnum were unaffected. These results show that differences in two physiological traits (growth rate and tolerance to flooding) among species, can explain when a peatland ecosystem shift might occur. In the last study, the function of peatlands was related to trade-offs between traits and allometric scaling in Sphagnum. Results suggested that growth strategies are determined by the distribution of Sphagnum relative to the water table in order to minimize periods with suboptimal hydration. Allometric analyses stressed the importance of resource allocation among and within shoots (apical part vs. stem), although the allocation patterns in Sphagnum were not always consistent with those of vascular plants. Interestingly, data indicated a trade-off between photosynthetic rate and decomposition rate among Sphagnum species.
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