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- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 2. |
- Di Angelantonio, Emanuele, et al.
(author)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Journal article (peer-reviewed)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 3. |
- Vishram-Nielsen, Julie K. K., et al.
(author)
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Does Estimated Pulse Wave Velocity Add Prognostic Information? : MORGAM Prospective Cohort Project
- 2020
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In: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 75:6, s. 1420-1428
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Journal article (peer-reviewed)abstract
- The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell's C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20-1.25] per m/s or 1.32 [1.29-1.34]), cardiovascular mortality (1.26 [1.21-1.32] or 1.35 [1.31-1.40]), and composite cardiovascular end point (1.19 [1.16-1.22] or 1.23 [1.20-1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08-1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91-1.03]) nor composite cardiovascular end point (1.10 [0.97-1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.
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