Restless legs syndrome is a common disease in the general population, affecting women more often than men. It is associated with reduced quality of life in cross-sectional analysis. Parity is a major factor in explaining the sex difference and may guide further clarification of the etiology of the disease.
Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. For a replication study, we selected 10 SNPs in six chromosomal regions with the strongest association (singly or as part of a haplotype) for retesting in an independent case-control set including 2,573 T2D cases and 2,776 controls. The most significant replicated result was found at the AHI1-LOC441171 gene region.
The pattern of linkage disequilibrium (LD) is critical for association studies, in which disease-causing variants are identified by allelic association with adjacent markers. The aim of this study is to compare the LD patterns in several distinct European populations. We analyzed four genomic regions (in total, 749 kb) containing candidate genes for complex traits. Individuals were genotyped for markers that are evenly distributed at an average spacing of approximately 2-4 kb in eight population-based samples from ongoing epidemiological studies across Europe. The Centre d'Etude du Polymorphisme Humain (CEPH) trios of the HapMap project were included and were used as a reference population. In general, we observed a conservation of the LD patterns across European samples. Nevertheless, shifts in the positions of the boundaries of high-LD regions can be demonstrated between populations, when assessed by a novel procedure based on bootstrapping. Transferability of LD information among populations was also tested. In two of the analyzed gene regions, sets of tagging single-nucleotide polymorphisms (tagSNPs) selected from the HapMap CEPH trios performed surprisingly well in all local European samples. However, significant variation in the other two gene regions predicts a restricted applicability of CEPH-derived tagging markers. Simulations based on our data set show the extent to which further gain in tagSNP efficiency and transferability can be achieved by increased SNP density.
Background and Purpose-Physical inactivity and unfavorable dietary and lifestyle patterns are related to cardiovascular disease and premature death. Their relationship to atherosclerosis of the carotid arteries and subsequent stroke is unclear. The objective of this study was to investigate the association between those behavioral cardiovascular risk factors and asymptomatic atherosclerosis of the carotid arteries in a population of former East Germany. Methods-The Study of Health in Pomerania (SHIP) is a cross-sectional survey in northeast Germany. In 1632 individuals aged 45 to 70 years, high-resolution B-mode ultrasound was used to assess the mean intima-media thickness of the right and left common carotid arteries. Carotid plaques and stenosis were recorded. Physical activity, dietary patterns, and cardiovascular risk factors were assessed in interviews with the use of standardized scales. Physically active participants with optimal dietary patterns were classified in the optimal lifestyle group, and those inactive with unfavorable diet were classified in the unfavorable group. Results-After adjustment for sex and age, significant decreasing trends were found for both intima-media thickness and severe asymptomatic atherosclerosis from unfavorable to optimal lifestyle patterns in never smokers but not in smokers.Regression analysis revealed an increased risk of severe asymptomatic atherosclerosis in subjects with an unfavorable lifestyle pattern compared with those with an optimal pattern (odds ratio 2.68; 95% CI, 1.13 to 6.37), following a significant linear trend. Conclusions-Physical activity and optimal diet are associated with reduced risk of early atherosclerosis in subjects who never smoked, while no benefit of an otherwise optimal lifestyle is observed in smokers.
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