| 1. |
- Palmer, Nicholette D, et al.
(author)
-
A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
-
In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
-
Journal article (peer-reviewed)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
|
|
| 2. |
- Saxena, Richa, et al.
(author)
-
Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
-
Journal article (peer-reviewed)abstract
- Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
|
|
| 3. |
- Scott, Robert A, et al.
(author)
-
No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels
- 2012
-
In: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296
-
Journal article (peer-reviewed)abstract
- Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
|
|
| 4. |
- Brunner, Eric, et al.
(author)
-
Social epidemiology and Eastern wisdom
- 2012
-
In: Journal of Epidemiology. - Fukuoka, Japan : Japan Epidemiological Association. - 0917-5040 .- 1349-9092. ; 22:4, s. 291-294
-
Research review (peer-reviewed)abstract
- Social epidemiology is the field of study that attempts to understand the social determinants of health and the dynamics between societal settings and health. In the past 3 decades, large-scale studies in the West have accumulated a range of measures and methodologies to pursue this goal. We would like to suggest that there may be conceptual gaps in the science if Western research models are applied uncritically in East Asian studies of socioeconomic, gender, and ethnic inequalities in health. On one hand, there are common concerns, including population aging and gendered labor market participation. Further, international comparison must be built on shared concepts such as socioeconomic stratification in market economies. On the other hand, some aspects of health, such as common mental disorders, may have culturally specific manifestations that require development of perspectives (and perhaps novel measures) in order to reveal Eastern specifics. Exploring and debating commonalities and differences in the determinants of health in Oriental and Occidental cultures could offer fresh inspiration and insight for the next phase of social epidemiology in both regions.
|
|
| 5. |
- Fransson, Eleonor, et al.
(author)
-
Association between change in body composition and change in inflammatory markers : An 11-year follow-up in the Whitehall II study
- 2010
-
In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 95:12, s. 5370-5374
-
Journal article (peer-reviewed)abstract
- Context: Obesity is associated with low-grade inflammation, but the long-term effects of weight change on inflammation are unknown.Objective: The aim was to examine the association of change in weight, body mass index (BMI), and waist circumference with change in C-reactive protein (CRP) and IL-6 and to assess whether this association is modified by baseline obesity status.Design and Setting: The design was a prospective cohort study among civil servants (the Whitehall II Study, UK). We used data from two clinical screenings carried out in 1991–1993 and 2002–2004 (mean follow-up, 11.3 yr).Participants: We studied 2496 men and 1026 women [mean age, 49.4 (SD = 6.0) yr at baseline] with measurements on inflammatory markers and anthropometry at both baseline and follow-up.Main Outcome Measures: We measured change in serum CRP and IL-6 during follow-up.Results: The mean increases in CRP and IL-6 were 0.08 [95% confidence interval (CI), 0.07–0.09] mg/liter and 0.04 (95% CI, 0.03–0.05) pg/ml per 1-kg increase in body weight during follow-up. Study members with a BMI less than 25 kg/m2 at baseline had an average increase in CRP of 0.06 (95% CI, 0.05–0.08) mg/liter per 1-kg increase in body weight, whereas the increase in those who were overweight (25 BMI < 30 kg/m2) and obese (BMI 30 kg/m2) was greater: 0.08 (95% CI, 0.06–0.09) mg/liter and 0.11 (95% CI, 0.07–0.14) mg/liter, respectively (P value for interaction = 0.002). Similar patterns were observed for changes in BMI and waist circumference.Conclusions: Those who were overweight or obese at baseline had a greater absolute increase in CRP per unit increase in weight, BMI, and waist circumference than people who were normal weight.
|
|
| 6. |
|
|
| 7. |
- Hiyoshi, Ayako, 1972-, et al.
(author)
-
A new theory-based social classification in Japan and its validation using historically collected information
- 2013
-
In: Social Science and Medicine. - Oxford, United Kingdom : Pergamon-Elsevier Ltd.. - 0277-9536 .- 1873-5347. ; 87, s. 84-92
-
Journal article (peer-reviewed)abstract
- Studies of health inequalities in Japan have increased since the millennium. However, there remains a lack of an accepted theory-based classification to measure occupation-related social position for Japan. This study attempts to derive such a classification based on the National Statistics Socio-economic Classification in the UK. Using routinely collected data from the nationally representative Comprehensive Survey of the Living Conditions of People on Health and Welfare, the Japanese Socioeconomic Classification was derived using two variables - occupational group and employment status. Validation analyses were conducted using household income, home ownership, self-rated good or poor health, and Kessler 6 psychological distress (n ≈ 36,000). After adjustment for age, marital status, and area (prefecture), one step lower social class was associated with mean 16% (p < 0.001) lower income, and a risk ratio of 0.93 (p < 0.001) for home ownership. The probability of good health showed a trend in men and women (risk ratio 0.94 and 0.93, respectively, for one step lower social class, p < 0.001). The trend for poor health was significant in women (odds ratio 1.12, p < 0.001) but not in men. Kessler 6 psychological distress showed significant trends in men (risk ratio 1.03, p = 0.044) and in women (1.05, p = 0.004). We propose the Japanese Socioeconomic Classification, derived from basic occupational and employment status information, as a meaningful, theory-based and standard classification system suitable for monitoring occupation-related health inequalities in Japan.
|
|
| 8. |
- Hiyoshi, Ayako, 1972-, et al.
(author)
-
Health inequalities in Japan : the role of material, psychosocial, social relational and behavioural factors
- 2014
-
In: Social Science and Medicine. - Oxford, United Kingdom : Pergamon-Elsevier Science Ltd. - 0277-9536 .- 1873-5347. ; 104, s. 201-209
-
Journal article (peer-reviewed)abstract
- The extent that risk factors, identified in Western countries, account for health inequalities in Japan remains unclear. We analysed a nationally representative sample (Comprehensive Survey of Living Conditions surveyed in 2001 (n = 40,243)). The cross-sectional association between self-rated fair or poor health and household income and a theory-based occupational social class was summarised using the relative index of inequality [RII]. The percentage attenuation in RII accounted for by candidate contributory factors - material, psychosocial, social relational and behavioural - was computed. The results showed that the RII for household income based on self-rated fair or poor health was reduced after including the four candidate contributory factors in the model by 20% (95% CI 2.1, 43.6) and 44% (95% CI 18.2, 92.5) in men and women, respectively. The RII for the Japanese Socioeconomic Classification [J-SEC] was reduced, not significantly, by 22% (95% CI -6.3, 100.0) in men in the corresponding model, while J-SEC was not associated with self-rated health in women. Material factors produced the most consistent and strong attenuation in RII for both socioeconomic indicators, while the contributions attributable to behaviour alone were modest. Social relational factors consistently attenuated the RII for both socioeconomic indicators in men whereas they did not make an independent contribution in women. The influence of perceived stress was inconsistent and depended on the socioeconomic indicator used. In summary, social inequalities in self-rated fair or poor health were reduced to a degree by the factors included. The results indicate that the levelling of health across the socioeconomic hierarchy needs to consider a wide range of factors, including material and psychosocial factors, in addition to the behavioural factors upon which the current public health policies in Japan focus. The analyses in this study need to be replicated using a longitudinal study design to confirm the roles of different factors in health inequalities.
|
|
| 9. |
- Hiyoshi, Ayako, 1972-, et al.
(author)
-
Inequalities in self-rated health in Japan 1986-2007 according to household income and a novel occupational classification : national sampling survey series
- 2013
-
In: Journal of Epidemiology and Community Health. - London, United Kingdom : BMJ Publishing Group. - 0143-005X .- 1470-2738. ; 67:11, s. 960-5
-
Journal article (peer-reviewed)abstract
- Background: Japan, for the past two decades, has seen economic stagnation and substantial social change. We examined whether health inequalities increased over this period.Methods: Using eight triennial waves of a series of large nationally representative surveys between 1986 and 2007 (n=398 303), temporal trends in relative and slope indices of inequality (RII, SII, respectively) were tested based on self-rated health in relation to theory-based social class and household income.Results: Age-standardised prevalence of self-rated fair or poor health showed V-shaped time trends in both sexes with the lowest prevalence in early/mid-1990s. In 1986, RII and SII in household social class and income were significant for both sexes. In men, RII and SII according to income showed significant narrowing of temporal trends in poor health (-1.4% and -0.1% annually, respectively), but these were stable in women. After multilevel multiple imputation for missing income data, the findings in men were not altered but narrowing trends became evident and significant in women (-1% and -0.1% annually, respectively). Inequality indices for social class remained constant over the study period in both sexes.Conclusions: Relative and absolute health inequalities for social class and income based on self-rated fair or poor health narrowed or remained stable between 1986 and 2007, despite the economic stagnation and adverse social changes. Overall population health across socioeconomic groups initially improved but then worsened. The positive finding regarding the health inequality trend seen in the Japanese context is informative for the wider international community during this period of economic uncertainty.
|
|
| 10. |
|
|
