| 1. |
- Ferrario, Marco M., et al.
(författare)
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Determinants of social inequalities in stroke incidence across Europe : a collaborative analysis of 126 635 individuals from 48 cohort studies
- 2017
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ PUBLISHING GROUP. - 0143-005X .- 1470-2738. ; 71:12, s. 1210-1216
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge on the origins of the social gradient in stroke incidence in different populations is limited. This study aims to estimate the burden of educational class inequalities in stroke incidence and to assess the contribution of risk factors in determining these inequalities across Europe.Materials and methods: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) Study comprises 48 cohorts recruited mostly in the 1980s and 1990s in four European regions using standardised procedures for baseline risk factor assessment and fatal and non-fatal stroke ascertainment and adjudication during follow-up. Among the 126 635 middle-aged participants, initially free of cardiovascular diseases, generating 3788 first stroke events during a median follow-up of 10 years, we estimated differences in stroke rates and HRs for the least versus the most educated individuals.Results: Compared with their most educated counterparts, the overall age-adjusted excess hazard for stroke was 1.54 (95% CI 1.25 to 1.91) and 1.41 (95% CI 1.16 to 1.71) in least educated men and women, respectively, with little heterogeneity across populations. Educational class inequalities accounted for 86–413 and 78–156 additional stroke events per 100 000 person-years in the least compared with most educated men and women, respectively. The additional events were equivalent to 47%–130% and 40%–89% of the average incidence rates. Inequalities in risk factors accounted for 45%–70% of the social gap in incidence in the Nordic countries, the UK and Lithuania-Kaunas (men), but for no more than 17% in Central and South Europe. The major contributors were cigarette smoking, alcohol intake and body mass index.Conclusions: Social inequalities in stroke incidence contribute substantially to the disease rates in Europe. Healthier lifestyles in the most disadvantaged individuals should have a prominent impact in reducing both inequalities and the stroke burden.
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| 2. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 3. |
- Veronesi, Giovanni, et al.
(författare)
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Combined effect of educational status and cardiovascular risk factors on the incidence of coronary heart disease and stroke in European cohorts : implications for prevention
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 24:4, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- Background: The combined effect of social status and risk factors on the absolute risk of cardiovascular disease has been insufficiently investigated, but results provide guidance on who could benefit most through prevention.Methods: We followed 77,918 cardiovascular disease-free individuals aged 35-74 years at baseline, from 38 cohorts covering Nordic and Baltic countries, the UK and Central Europe, for a median of 12 years. Using Fine-Gray models in a competing-risks framework we estimated the effect of the interaction of education with smoking, blood pressure and body weight on the cumulative risk of incident acute coronary heart disease and stroke.Results: Compared with more educated smokers, the less educated had an added increase in absolute risk of cardiovascular disease of 3.1% ( 95% confidence interval+0.1%, +6.2%) in men and of 1.5% ( = 1.9%, +5.0%) in women, consistent across smoking categories. Conversely, the interaction was negative for overweight: -2.6% ( 95% CI: -5.6%, +0.3%) and obese: -3.6% ( -7.6%, +0.4%) men, suggesting that the more educated would benefit more from the same reduction in body weight. A weaker interaction was observed for body weight in women, and for blood pressure in both genders. Less educated men and women with a cluster of two or more risk factors had an added cardiovascular disease risk of 3.6% ( +0.1%, +7.0%) and of 2.6% ( - 0.5%, +5.6%), respectively, compared with their more educated counterparts.Conclusions: Socially disadvantaged subjects have more to gain from lifestyle and blood pressure modification, hopefully reducing both their risk and also social inequality in disease.
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