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- Lindgren, Cecilia M, et al.
(författare)
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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
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- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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- Scott, Robert A, et al.
(författare)
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No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels
- 2012
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Ingår i: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296
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Tidskriftsartikel (refereegranskat)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.
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- Holloway, A., et al.
(författare)
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EVALUATING GLOBAL PATTERNS IN TREATMENT AND PREVALENCE OF COMORBIDITIES IN SYSTEMIC LUPUS ERYTHEMATOSUS
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1456-1458
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Regional disparities in the management of systemic lupus erythematosus (SLE) are frequently described. Governance, funding, logistic barriers, and physician choice may be important determinants though scarce data from underrepresented regions limits our understanding.Objectives: To evaluate global patterns in treatment of SLE and identify the prevalence of comorbidities.Methods: We identified SLE patients from the COVAD 2 database, consisting of over 20,000 respondents worldwide. Healthy controls (HC) were included to assess population comorbidity levels. Demographics, treatment i.e., corticosteroids (CS), antimalarials, immunosuppressants (IS), cyclophosphamide and biologics plus comorbidity data was recorded. Country Human Development Index (HDI) classification, a composite index formulated by the United Nations to rank countries into tiers of development, was utilised.Results: 3323 HCs and 1167 SLE patients were included in analysis. Patients from low/medium HDI (lmHDI) countries were younger than those from high/very high HDI (hvhHDI) countries (median age 32, IQR 27-41 vs 41, IQR 32-52 years, p<0.0001). Disease duration was shorter in lmHDI countries (median 5, IQR 3-10 vs 10, IQR 5-19 years, p<0.0001).A higher proportion of SLE patients from lmHDI countries were on CS (73% vs 59%, p=0.0002), antimalarials (81% vs 68%, p=0.0002) and IS (66% vs 53%, p=0.0009) compared with patients from hvhHDI countries. Choice of IS varied with azathioprine prescribed more frequently in lmHDI countries (p=0.049). Biologics use was more common in hvhHDI countries (7% vs 2%, p=0.0055). Comorbidity prevalence was similar between groups, however when adjusted for age, patients with chronic kidney disease were significantly younger in lmHDI countries (36.67 vs 44.64 years, p=0.015), as were patients with coronary artery disease (35.7 vs. 44.6 years, p=0.015) and hypertension (41.5 vs 49.8 years, p=0.003). Results are detailed in Table 1.Conclusion: To our knowledge, this is the largest study evaluating treatment and comorbidity incidence in SLE populations based on country HDI. We identified striking differences in pharmacological management globally. Cardiovascular comorbidities were seen in younger patients and earlier in the disease course in lmHDI countries, suggestive of premature organ damage. This could be due to limited global access to high-cost medication and increasing access may improve outcomes. Our results call for review of cardiovascular risk guidelines and regional approaches to preventive action as well as pharmacological and non-pharmacological management of patients with established cardiovascular comorbidity.
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