| 11. |
- Modin, Bitte, 1962-
(författare)
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Setting the scene for life. Longitudinal studies of early social disadvantage and later life chances : Department of Sociology
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the long-term life chances of children brought up under various conditions in Sweden during the first half of the twentieth century. The main purpose is to examine the consequences of children’s early family environment for later educational career, and ultimately, for their mortality risk at different stages of the life-course. Two aspects of family structure are focused upon: the birth order of the subject and the mother’s marital status at the time of childbirth. The four studies are all based on the 14,192 babies that were born alive at the Uppsala Academic Hospital during the period 1915–29. Nearly all these children (97.3 percent) have been successfully followed up in parish archives and later through computerised linking to census and death registries. While social class is probably one of the most commonly used indicators of childhood social conditions, the two measures of family structure used here may be assumed to capture additional aspects of childhood social circumstances in ways that differ from that of the social structure position of the parent(s). However, social class and certain biological conditions at the time of birth are also taken into consideration in the analyses as well as several indicators of adult social circumstances.The results showed that third grade school marks worsened steadily with increasing birth order, whereas children who were born outside marriage did not manage significantly worse than those who were born inside marriage. As for achieved education, the chance of having completed upper secondary school declined dramatically with increasing birth order, and was significantly lower for subjects born outside marriage than for those who were born inside marriage. Also with regard to birth order patterns of all cause mortality in four stages of the life-course (infancy, childhood, adulthood and middle to old age) the overall picture pointed towards laterborns being at a disadvantage throughout the studied age intervals. The analyses suggested that adult socio-economic status served as a mediating variable in the association between childhood birth order position and adult mortality.Another potential mediator between conditions in early life and later mortality is ‘marital career’. A recent study found that men who were small at birth were less likely to marry. Based on these findings the authors proposed that the link between marital status and cardiovascular disease could have its origins in intrauterine life. A replication of this study verified the link between fetal growth and subsequent marital status for men, but not for women. However, the results did not support the suggestion that growth rate in utero could explain why unmarried people have higher death rates. The final study examines whether the mother’s marital status at the time of childbirth is associated with her son’s long-term risk of ischaemic heart disease mortality, and whether any such association works via these men’s own marital status in adulthood. The results demonstrated a significant excess IHD mortality among men born outside marriage, which was largely explained by the mortality risk among those men born outside wedlock and who never married being over twice as high as that of the corresponding group of men born to married parents.
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| 12. |
- Ong, Ken K., et al.
(författare)
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Genetic variation in LIN28B is associated with the timing of puberty
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:6, s. 729-733
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Tidskriftsartikel (refereegranskat)abstract
- The timing of puberty is highly variable(1). We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 x 10(-10); combined P = 3.6 x 10(-16)). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 x 10(-7); N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing(2), as the first genetic determinant regulating the timing of human pubertal growth and development.
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| 13. |
- Power, Chris, et al.
(författare)
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The contribution of childhood and adult socioeconomic position to adult obesity and smoking behaviour : an international comparison
- 2005
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 34:2, s. 335-344
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Our objective was to investigate the contribution of childhood and adult socioeconomic position (SEP) to adult obesity and smoking behaviour, in particular to establish the role of childhood circumstances across different studies in Europe and the US.METHODS:Seven population-based surveys in six Western countries (Britain, Denmark, Finland, Netherlands, Sweden, US) were examined, with participants aged 30-50 yr and born between 1910 and 1960. Adult smoking was analysed using three outcomes (ever, current, or ex-) and adult obesity was defined as body mass index (kg/m(2)) > or =30.RESULTS:A strong effect of adult social position was observed for smoking outcomes and obesity. For example, manual SEP in adulthood increased the risk of ever smoking (adjusted odds ratio (OR) 1.47-2.00 for men; 0.94-1.81 for women), and obesity (adjusted OR 1.06-2.24 for men, 1.21-3.26 for women). In most studies, childhood position was not associated with ever-smoking. For current smoking, manual childhood position was associated among women (adjusted OR 1.09-1.54), but no consistent pattern was seen for men. For ex-smoking, manual childhood origins lowered the chance of quitting among women (adjusted OR 0.64-0.81) except in the US (OR = 1.17); among men this association was seen in fewer studies (adjusted OR 0.74-1.09). For obesity, manual origins increased the risk for women (adjusted OR 0.96-2.50); effects were weaker among men but mostly in the same direction (adjusted OR 0.79-1.42).CONCLUSIONS:As expected, adult SEP was an important influence on smoking behaviour and obesity. In addition, factors related to disadvantaged social origins appeared to increase the risk of obesity and reduce the probability of quitting smoking in adulthood, particularly in women.
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| 14. |
- 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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| 15. |
- Settersten, Richard A., et al.
(författare)
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Understanding the effects of Covid-19 through a life course lens
- 2020
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Ingår i: Advances in Life Course Research. - : Elsevier BV. - 1040-2608. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- The Covid-19 pandemic is shaking fundamental assumptions about the human life course in societies around the world. In this essay, we draw on our collective expertise to illustrate how a life course perspective can make critical contributions to understanding the pandemic's effects on individuals, families, and populations. We explore the pandemic's implications for the organization and experience of life transitions and trajectories within and across central domains: health, personal control and planning, social relationships and family, education, work and careers, and migration and mobility. We consider both the life course implications of being infected by the Covid-19 virus or attached to someone who has; and being affected by the pandemic's social, economic, cultural, and psychological consequences. It is our goal to offer some programmatic observations on which life course research and policies can build as the pandemic's short- and long-term consequences unfold.
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| 16. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 17. |
- Tikhonoff, Valérie, et al.
(författare)
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The relationship between affective symptoms and hypertension-role of the labelling effect: the 1946 British birth cohort.
- 2016
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Ingår i: Open heart. - : BMJ. - 2053-3624. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the association between repeated measures of affective symptoms collected over 2 decades and hypertension (clinically ascertained or self-report); to test whether, among people with hypertension, affective symptoms are associated with awareness of hypertension, and to evaluate the longitudinal effects of the label of hypertension on affective symptoms.Multivariable logistic regression, accounting for confounders and mediators, were used to test the aforementioned associations in 1683 participants from a national British cohort.Weak evidence of a cumulative impact of affective symptoms across adulthood on self-reported hypertension at age 60-64years was observed (OR 1.40 (95% CI 1.10 to 1.78) and 1.19 (0.79 to 1.80) for symptoms at 1-2 time points and at 3-4 time points vs no symptoms, respectively). Study members with affective symptoms in recent times were more likely to have self-reported hypertension at age 60-64years than those without symptoms (OR 1.47 (1.10 to 1.96)). Similar results were observed for awareness of hypertension (OR 2.00 (1.30 to 3.06)). Conversely, no associations were found with clinically ascertained hypertension. The act of labelling someone as hypertensive at age 53years was associated with affective symptoms at age 60-64years, independently of antihypertensive treatment and affective symptoms at the time of the diagnosis (OR 2.40 (1.32 to 4.36)).Our findings suggest that elevated risk of hypertension in participants with affective symptoms might be explained by awareness of hypertension and by exposure to medical attention, though not by a direct effect of affective symptoms on blood pressure. Conversely, long-term psychological consequences of the label of hypertension are observed.
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| 18. |
- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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| 19. |
- Wheeler, Eleanor, et al.
(författare)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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| 20. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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