| 1. |
- Fall, Tove, et al.
(författare)
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Age- and sex-specific causal effects of adiposity on cardiovascular risk factors
- 2015
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:5, s. 1841-1852
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Tidskriftsartikel (refereegranskat)abstract
- Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.
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| 2. |
- Howe, Laurence J., et al.
(författare)
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Educational attainment, health outcomes and mortality : a within-sibship Mendelian randomization study
- 2023
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Ingår i: International Journal of Epidemiology. - 0300-5771 .- 1464-3685. ; 52:5, s. 1579-1591
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. Methods Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. Results Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. Conclusions These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.
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| 3. |
- Jelenkovic, Aline, et al.
(författare)
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Associations between birth size and later height from infancy through adulthood : An individual based pooled analysis of 28 twin cohorts participating in the CODATwins project
- 2018
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Ingår i: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 120, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14–4.25 cm and 0.18–0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight.
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| 4. |
- Jelenkovic, Aline, et al.
(författare)
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Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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| 5. |
- Kilpi, Fanny, et al.
(författare)
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Disentangling the relative importance of different socioeconomic resources for myocardial infarction incidence and survival : a longitudinal study of over 300 000 Finnish adults
- 2016
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 26:2, s. 260-266
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lower socioeconomic position (SEP) is associated with an increased risk of myocardial infarction (MI) incidence and mortality, but the relative importance of different socioeconomic resources at different stages of the disease remains unclear. Methods: A nationally representative register-based sample of 40- to 60-year-old Finnish men and women in 1995 (n = 302 885) were followed up for MI incidence and mortality in 1996-2007. We compared the effects of education, occupation, income and wealth on first MI incidence, first-day and long-term fatality. Cox's proportional hazards regression and logistic regression models were estimated adjusting for SEP covariates simultaneously to assess independent effects. Results: Fully adjusted models showed greatest relative inequalities of MI incidence by wealth in both sexes, with an increased risk also associated with manual occupations. Education was a significant predictor of incidence in men. Low income was associated with a greater risk of death on the day of MI incidence [odds ratio (OR) = 1.40 in men and 1.95 in women when comparing lowest and highest income quintiles], and in men, with long-term fatality [hazard ratio (HR) = 1.74]. Wealth contributed to inequalities in first-day fatality in men and in long-term fatality in both sexes. Conclusion: The results show that different socioeconomic resources have diverse effects on the disease process and add new evidence on the significant association of wealth with heart disease onset and fatality. Targeting those with the least resources could improve survival in MI patients and help reduce social inequalities in coronary heart disease mortality.
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| 6. |
- Kilpi, Fanny, et al.
(författare)
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Early-life and adult socioeconomic determinants of myocardial infarction incidence and fatality
- 2017
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 177, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- Social inequalities in coronary heart disease mortality have roots in childhood conditions, but it is unknown whether they are associated both with the incidence of the disease and the following survival. We studied how several different early-life socioeconomic factors, together with later socioeconomic attainment, were associated with myocardial infarction (MI) incidence and fatality in Finland. The data was based on a register-based sample of households from a census in 1950 that also provided information on childhood circumstances. MI hospitalizations and mortality in 1988-2010 were studied in those who were up to 14 years of age at the time of the census and resident in Finland in 1987 (n = 94,501). Parental education, occupation, household crowding, home ownership, and family type were examined together with adulthood education and income. Hazard and odds ratios with 95% confidence intervals (CI) were calculated using Cox regression (incidence and long-term fatality) and logistic regression (short-term fatality) models. Lower parental education, occupational background and greater household crowding were associated with MI incidence. In models adjusted for adulthood variables, crowding increased the risk by 16% (95% CI 5-29%) in men and 25% (95% CI 3-50%) in women. Shortterm survival was more favourable in sons of white-collar parents and daughters of owner-occupied households, but most aspects of childhood circumstances did not strongly influence long-term fatality risk. Socioeconomic attainment in adulthood accounted for a substantial part of the effects of childhood conditions, but the measured childhood factors explained little of the disparities by adulthood education and income. Moreover, income and education remained associated with MI incidence when adjusted for unobserved shared family factors in siblings. Though social and economic development in society seems to have mitigated the disease burden associated with poor childhood living conditions in Finland, low adult socioeconomic resources have remained a strong determinant of MI incidence and fatality.
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| 7. |
- Kilpi, Fanny, et al.
(författare)
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Reply to Oude Groeniger and van Lenthe
- 2018
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Ingår i: Epidemiology. - 1044-3983 .- 1531-5487. ; 29:4, s. e37-e37
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Kilpi, Fanny, et al.
(författare)
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The Spillover Influence of Partner’s Education on Myocardial Infarction Incidence and Survival
- 2018
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Ingår i: Epidemiology. - 1044-3983 .- 1531-5487. ; 29:2, s. 237-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Education is believed to have positive spillover effects across network connections. Partner’s education may be an important resource preventing the incidence of disease and helping patients cope with illness. We examined how partner’s education predicted myocardial infarction (MI) incidence and survival net of own education and other socioeconomic resources in Finland.Methods: A sample of adults aged 40–69 years at baseline in Finland in 1990 was followed up for MI incidence and mortality during the period 1991–2007 (n = 354,100).Results: Lower own and spousal education both contributed independently to a higher risk of MI incidence and fatality when mutually adjusted. Having a partner with basic education was particularly strongly associated with long-term fatality in women with a hazard ratio of 1.53 (95% confidence interval, 1.22–1.92) compared with women with tertiary level educated partners. There was some evidence that the incidence risk associated with basic spousal education was weaker in those with own basic education. The highest risks of MI incidence and fatality were consistently found in those without a partner, whereas the most favorable outcomes were in households where both partners had a tertiary level of education.Conclusions: Accounting for spousal education demonstrates how health-enhancing resources accumulate to some households. Marriage between people of similar educational levels may therefore contribute to the widening of educational differences in MI incidence and survival.
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| 9. |
- Martikainen, Pekka, et al.
(författare)
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Joint association between education and polygenic risk score for incident coronary heart disease events : a longitudinal population-based study of 26 203 men and women
- 2021
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 75:7, s. 651-657
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Tidskriftsartikel (refereegranskat)abstract
- Background Genetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.Methods The data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.Results Allowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.Conclusions PRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.
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| 10. |
- Narusyte, Jurgita, et al.
(författare)
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Genetic Liability to Disability Pension in Women and Men: A Prospective Population-Based Twin Study
- 2011
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies of risk factors for disability pension (DP) have mainly focused on psychosocial, or environmental, factors, while the relative importance of genetic effects has been less studied. Sex differences in biological mechanisms have not been investigated at all.Methods: The study sample included 46,454 Swedish twins, consisting of 23,227 complete twin pairs, born 1928–1958, who were followed during 1993–2008. Data on DP, including diagnoses, were obtained from the National Social Insurance Agency. Within-pair similarity in liability to DP was assessed by calculating intraclass correlations. Genetic and environmental influences on liability to DP were estimated by applying discrete-time frailty modeling.Results: During follow-up, 7,669 individuals were granted DP (18.8% women and 14.1% men). Intraclass correlations were generally higher in MZ pairs than DZ pairs, while DZ same-sexed pairs were more similar than opposite-sexed pairs. The best-fitting model indicated that genetic factors contributed 49% (95% CI: 39–59) to the variance in DP due to mental diagnoses, 35% (95% CI: 29–41) due to musculoskeletal diagnoses, and 27% (95% CI: 20–33) due to all other diagnoses. In both sexes, genetic effects common to all ages explained one-third, whereas age-specific factors almost two-thirds, of the total variance in liability to DP irrespective of diagnosis. Sex differences in liability to DP were indicated, in that partly different sets of genes were found to operate in women and men, even though the magnitude of genetic variance explained was equal for both sexes.Conclusions: The findings of the study suggest that genetic effects are important for liability to DP due to different diagnoses. Moreover, genetic contributions to liability to DP tend to differ between women and men, even though the overall relative contribution of genetic influences does not differ by sex. Hence, the pathways leading to DP might differ between women and men.
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