| 1. |
- Stevens, Kristen N, et al.
(författare)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
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Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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| 2. |
- Kirchhoff, Tomas, et al.
(författare)
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Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
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| 3. |
- Smedby, Karin E., et al.
(författare)
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GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:4, s. e1001378-
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, P-combined= 2x10(-21)) located 962 bp away from rs10484561 (r(2)< 0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012: ORadjusted = 0.70, P-adjusted= 4x10(-12); rs10484561: ORadjusted = 1.64, P-adjusted= 5x10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, P-combined = 1.4x10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.
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| 4. |
- Conde, Lucia, et al.
(författare)
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Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:8, s. 661-664
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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| 5. |
- Humphreys, Aelys M., et al.
(författare)
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Evidence for recent evolution of cold tolerance in grasses suggests current distribution is not limited by (low) temperature
- 2013
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 198:4, s. 1261-1273
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Tidskriftsartikel (refereegranskat)abstract
- Temperature is considered an important determinant of biodiversity distribution patterns. Grasses (Poaceae) occupy among the warmest and coldest environments on earth but the role of cold tolerance evolution in generating this distribution is understudied. We studied cold tolerance of Danthonioideae (c. 280 species), a major constituent of the austral temperate grass flora. We determined differences in cold tolerance among species from different continents grown in a common winter garden and assessed the relationship between measured cold tolerance and that predicted by species ranges. We then used temperatures in current ranges and a phylogeny of 81% of the species to study the timing and mode of cold tolerance evolution across the subfamily. Species ranges generally underestimate cold tolerance but are still a meaningful representation of differences in cold tolerance among species. We infer cold tolerance evolution to have commenced at the onset of danthonioid diversification, subsequently increasing in both pace and extent in certain lineages. Interspecific variation in cold tolerance is better accounted for by spatial than phylogenetic distance. Contrary to expectations, temperature low temperature in particular appears not to limit the distribution of this temperate clade. Competition, time or dispersal limitation could explain its relative absence from northern temperate regions.
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| 6. |
- Kross, Angela S. E., et al.
(författare)
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Phenology and its role in carbon dioxide exchange processes in northern peatlands
- 2014
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Ingår i: Journal of Geophysical Research - Biogeosciences. - 2169-8953. ; 119:7, s. 1370-1384
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Tidskriftsartikel (refereegranskat)abstract
- Ecosystem phenology plays an important role in carbon exchange processes and can be derived from continuous records of carbon dioxide (CO2) exchange data. In this study we examined the potential use of phenological indices for characterizing cumulative annual CO2 exchange in four contrasting northern peatland ecosystems. We used the approach of Jonsson and Eklundh (2004) to derive a set of phenological indices based on the daily time series of gross primary production (GPP), ecosystem respiration (R-e), and net ecosystem production (NEP) measured in the four peatland sites. The main objectives of this study were (a) to examine the variation in phenological indices across sites and (b) to determine the relationships among phenological indices, environmental conditions, and cumulative annual CO2 exchange. The phenological index used to define the "start of the growing season" showed good potential for differentiation among sites based on their average annual site GPP. Sites with earlier growing seasons had the highest average annual site GPP. The "peak CO2 exchange rate" phenological index performed best in reflecting variations among sites and for estimating annual values of GPP, R-e, and NEP (Pearson correlation coefficients ranged between 0.77 and 0.99, p<0.05 for all.). The phenological indices and annual GPP, R-e, and NEP were sensitive to winter (January-March) and summer (July-September) temperature and precipitation, but correlations, though significant, were weak.
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| 7. |
- Leu, Monica, et al.
(författare)
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NordicDB : a Nordic pool and portal for genome-wide control data
- 2010
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 18:12, s. 1322-1326
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Tidskriftsartikel (refereegranskat)abstract
- A cost-efficient way to increase power in a genetic association study is to pool controls from different sources. The genotyping effort can then be directed to large case series. The Nordic Control database, NordicDB, has been set up as a unique resource in the Nordic area and the data are available for authorized users through the web portal (http://www.nordicdb.org). The current version of NordicDB pools together high-density genome-wide SNP information from similar to 5000 controls originating from Finnish, Swedish and Danish studies and shows country-specific allele frequencies for SNP markers. The genetic homogeneity of the samples was investigated using multidimensional scaling (MDS) analysis and pairwise allele frequency differences between the studies. The plot of the first two MDS components showed excellent resemblance to the geographical placement of the samples, with a clear NW-SE gradient. We advise researchers to assess the impact of population structure when incorporating NordicDB controls in association studies. This harmonized Nordic database presents a unique genome-wide resource for future genetic association studies in the Nordic countries. European Journal of Human Genetics (2010) 18, 1322-1326; doi: 10.1038/ejhg.2010.112; published online 28 July 2010
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| 8. |
- Linder, H. Peter, et al.
(författare)
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What determines biogeographical ranges? : Historical wanderings and ecological constraints in the danthonioid grasses
- 2013
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 40:5, s. 821-834
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Tidskriftsartikel (refereegranskat)abstract
- Aim We sought to understand the variables that limit the distribution range of a clade (here the danthonioid grasses). We tested time, area of origin, habitat suitability, disjunction width and nature, and wind direction as possible range determinants. Location Global, but predominantly the Southern Hemisphere. Methods We mapped the range of the subfamily Danthonioideae, and used 39,000 locality records and an ensemble modelling approach to define areas with suitable danthonioid habitat. We used a well-sampled, dated phylogeny to estimate the number and direction of historical dispersal events, based on parsimony optimization. We tested for the impact of wind direction on dispersal rate using a likelihood approach, and for the effects of barrier width with a regression approach. Results We found 17 geographically isolated areas with suitable habitats for danthonioids. All currently suitable Southern Hemisphere areas have been occupied, but three apparently suitable areas in the Northern Hemisphere have not. We infer that southern Africa was first occupied in the Oligocene and that dispersal to the other areas was initiated in the middle Miocene. Inferred dispersal rate was correlated with the width of the disjunctions, up to a distance of 5000km. There was no support for wind direction having influenced differences in dispersal rate. Main conclusions The current range of the Danthonioideae can be predicted ecologically (areas with suitable habitat) and historically (the width of the disjunctions separating the areas with suitable habitat and the area of origin). The direction of dispersal is dictated by the area of origin and by serendipity: there is no evidence for general patterns of dispersal, for example for dispersal occurring more frequently over land than over sea or in an easterly versus a westerly direction around the Southern Hemisphere. Thus the range and range-filling of Danthonioideae can be accounted for by surprisingly few variables: habitat suitability, distance between suitable areas, and area of origin.
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| 9. |
- Lund, Magnus, et al.
(författare)
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Variability in exchange of CO2 across 12 northern peatland and tundra sites
- 2010
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 16:9, s. 2436-2448
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Tidskriftsartikel (refereegranskat)abstract
- Many wetland ecosystems such as peatlands and wet tundra hold large amounts of organic carbon (C) in their soils, and are thus important in the terrestrial C cycle. We have synthesized data on the carbon dioxide (CO2) exchange obtained from eddy covariance measurements from 12 wetland sites, covering 1-7 years at each site, across Europe and North America, ranging from ombrotrophic and minerotrophic peatlands to wet tundra ecosystems, spanning temperate to arctic climate zones. The average summertime net ecosystem exchange of CO2 (NEE) was highly variable between sites. However, all sites with complete annual datasets, seven in total, acted as annual net sinks for atmospheric CO2. To evaluate the influence of gross primary production (GPP) and ecosystem respiration (R-eco) on NEE, we first removed the artificial correlation emanating from the method of partitioning NEE into GPP and R-eco. After this correction neither R-eco (P = 0.162) nor GPP (P = 0.110) correlated significantly with NEE on an annual basis. Spatial variation in annual and summertime R-eco was associated with growing season period, air temperature, growing degree days, normalized difference vegetation index and vapour pressure deficit. GPP showed weaker correlations with environmental variables as compared with R-eco, the exception being leaf area index (LAI), which correlated with both GPP and NEE, but not with R-eco. Length of growing season period was found to be the most important variable describing the spatial variation in summertime GPP and R-eco; global warming will thus cause these components to increase. Annual GPP and NEE correlated significantly with LAI and pH, thus, in order to predict wetland C exchange, differences in ecosystem structure such as leaf area and biomass as well as nutritional status must be taken into account.
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