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- Surendran, Praveen, et al.
(författare)
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Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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| 2. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 3. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 4. |
- Hajdarevic, Senada, 1970-, et al.
(författare)
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Awareness of sunburn in childhood, use of sunbeds and change of moles in Denmark, Northern Ireland, Norway and Sweden
- 2016
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 26:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malignant melanoma (MM) is increasing rapidly in Northern Europe. To reduce incidence and mortality through earlier diagnosis, public awareness of MM is important. Thus, we aim to examine awareness of risk factors and a symptom of MM, and how awareness varies by country and socio-demographic factors in Denmark, Northern Ireland (NI), Norway and Sweden.METHODS: Population-based telephone interviews using the 'Awareness and Beliefs about Cancer' measure were conducted in 2011 among 8355 adults ≥50 years as part of the International Cancer Benchmarking Partnership Module 2. Prevalence ratios (PRs) with 95% confidence intervals were calculated.RESULTS: In these four countries, lowest awareness was found for 'sunburn in childhood' (63%), whereas awareness was high for 'use of sunbeds' (91%) and 'mole change' (97%). Lack of awareness of 'sunburn in childhood' was more prevalent among respondents from Norway [PR = 1.38 (1.28-1.48)] but less prevalent among respondents from Northern Ireland (NI) [PR = 0.78 (0.72-0.85)] and Sweden [PR = 0.86 (0.79-0.93)] compared with respondents from Denmark. Lack of awareness of 'use of sunbeds' was more prevalent among respondents from Norway [PR = 2.99 (2.39-3.74)], Sweden [PR = 1.57 (1.22-2.00)], and NI [PR = 1.65 (1.30-2.10)] compared with respondents form Denmark. Being a man, age ≥70, living alone, and having lower education, were each independently associated with lack of MM-awareness.CONCLUSIONS: The results indicate relatively low awareness of 'sunburn in childhood' as a risk factor for MM, and important disparities in MM-awareness across countries and socio-demographic groups. Improved and more directed initiatives to enhance public MM-awareness, particularly about 'sunburn in childhood', are needed.
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| 5. |
- Hvidberg, Line, et al.
(författare)
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Awareness of cancer symptoms and anticipated patient interval for healthcare seeking. A comparative study of Denmark and Sweden
- 2016
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:7, s. 917-924
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Tidskriftsartikel (refereegranskat)abstract
- Background Recent epidemiologic data show that Denmark has considerably poorer survival from common cancers than Sweden. This may be related to a lower awareness of cancer symptoms and longer patient intervals in Denmark than in Sweden. The aims of this study were to: 1) compare population awareness of three possible symptoms of cancer (unexplained lump or swelling, unexplained bleeding and persistent cough or hoarseness); 2) compare anticipated patient interval when noticing any breast changes, rectal bleeding and persistent cough; and 3) examine whether potential differences were noticeable in particular age groups or at particular levels of education in a Danish and Swedish population sample.Method Data were derived from Module 2 of the International Cancer Benchmarking Partnership. Telephone interviews using the Awareness and Beliefs about Cancer measure were conducted in 2011 among 3000 adults in Denmark and 3070 adults in Sweden.Results Danish respondents reported a higher awareness of two of three symptoms (i.e. unexplained lump or swelling and persistent cough or hoarseness) and a shorter anticipated patient interval for two of three symptoms studied (i.e. any breast changes and rectal bleeding) than Swedish respondents. Differences in symptom awareness and anticipated patient interval between these countries were most pronounced in highly educated respondents.Conclusion Somewhat paradoxically, the highest awareness of symptoms of cancer and the shortest anticipated patient intervals were found in Denmark, where cancer survival is lower than in Sweden. Thus, it appears that these differences in symptom awareness and anticipated patient interval do not help explain the cancer survival disparity between Denmark and Sweden.
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