Is the prevalence of overactive bladder overestimated? : A population-based study in Finland

Background. In earlier studies, one in six adults had overactive bladder which may impair quality of life. However, earlier studies have either not been population-based or have suffered from methodological limitations. Our aim was to assess the prevalence of overactive bladder symptoms, based on a representative study population and using consistent definitions and exclusions. Methodology/Principal Findings. The aim of the study was to assess the age-standardized prevalence of overactive bladder defined as urinary urgency, with or without urgency incontinence, usually with urinary frequency and nocturia in the absence of urinary tract infection or other obvious pathology. In 2003-2004, a questionnaire was mailed to 6,000 randomly selected Finns aged 18-79 years who were identified from the Finnish Population Register Centre. Information on voiding symptoms was collected using the validated Danish Prostatic Symptom Score, with additional frequency and nocturia questions. Corrected prevalence was calculated with adjustment for selection bias due to non-response. The questionnaire also elicited co-morbidity and socio-demographic information. Of the 6,000 subjects, 62.4% participated. The prevalence of overactive bladder was 6.5% (95% CI, 5.5% to 7.6%) for men and 9.3% (CI, 7.9% to 10.6%) for women. Exclusion of men with benign prostatic hyperplasia reduced prevalence among men by approximately one percentage point (to 5.6% [CI, 4.5% to 6.6%]). Among subjects with overactive bladder, urgency incontinence, frequency, and nocturia were reported by 11%, 23%, and 56% of men and 27%, 38%, and 40% of women, respectively. However, only 31% of men and 35% of women with frequency, and 31% of subjects of both sexes with nocturia reported overactive bladder. Conclusions/Significance. Our results indicate a prevalence of overactive bladder as low as 8% suggesting that, in previous studies, occurrence has been overestimated due to vague criteria and selected study populations regarding age distribution and low participation.Background. In earlier studies, one in six adults had overactive bladder which may impair quality of life. However, earlier studies have either not been population-based or have suffered from methodological limitations. Our aim was to assess the prevalence of overactive bladder symptoms, based on a representative study population and using consistent definitions and exclusions. Methodology/Principal Findings. The aim of the study was to assess the age-standardized prevalence of overactive bladder defined as urinary urgency, with or without urgency incontinence, usually with urinary frequency and nocturia in the absence of urinary tract infection or other obvious pathology. In 2003-2004, a questionnaire was mailed to 6,000 randomly selected Finns aged 18-79 years who were identified from the Finnish Population Register Centre. Information on voiding symptoms was collected using the validated Danish Prostatic Symptom Score, with additional frequency and nocturia questions. Corrected prevalence was calculated with adjustment for selection bias due to non-response. The questionnaire also elicited co-morbidity and socio-demographic information. Of the 6,000 subjects, 62.4% participated. The prevalence of overactive bladder was 6.5% (95% CI, 5.5% to 7.6%) for men and 9.3% (CI, 7.9% to 10.6%) for women. Exclusion of men with benign prostatic hyperplasia reduced prevalence among men by approximately one percentage point (to 5.6% [CI, 4.5% to 6.6%]). Among subjects with overactive bladder, urgency incontinence, frequency, and nocturia were reported by 11%, 23%, and 56% of men and 27%, 38%, and 40% of women, respectively. However, only 31% of men and 35% of women with frequency, and 31% of subjects of both sexes with nocturia reported overactive bladder. Conclusions/Significance. Our results indicate a prevalence of overactive bladder as low as 8% suggesting that, in previous studies, occurrence has been overestimated due to vague criteria and selected study populations regarding age distribution and low participation.Background. In earlier studies, one in six adults had overactive bladder which may impair quality of life. However, earlier studies have either not been population-based or have suffered from methodological limitations. Our aim was to assess the prevalence of overactive bladder symptoms, based on a representative study population and using consistent definitions and exclusions. Methodology/Principal Findings. The aim of the study was to assess the age-standardized prevalence of overactive bladder defined as urinary urgency, with or without urgency incontinence, usually with urinary frequency and nocturia in the absence of urinary tract infection or other obvious pathology. In 2003-2004, a questionnaire was mailed to 6,000 randomly selected Finns aged 18-79 years who were identified from the Finnish Population Register Centre. Information on voiding symptoms was collected using the validated Danish Prostatic Symptom Score, with additional frequency and nocturia questions. Corrected prevalence was calculated with adjustment for selection bias due to non-response. The questionnaire also elicited co-morbidity and socio-demographic information. Of the 6,000 subjects, 62.4% participated. The prevalence of overactive bladder was 6.5% (95% CI, 5.5% to 7.6%) for men and 9.3% (CI, 7.9% to 10.6%) for women. Exclusion of men with benign prostatic hyperplasia reduced prevalence among men by approximately one percentage point (to 5.6% [CI, 4.5% to 6.6%]). Among subjects with overactive bladder, urgency incontinence, frequency, and nocturia were reported by 11%, 23%, and 56% of men and 27%, 38%, and 40% of women, respectively. However, only 31% of men and 35% of women with frequency, and 31% of subjects of both sexes with nocturia reported overactive bladder. Conclusions/Significance. Our results indicate a prevalence of overactive bladder as low as 8% suggesting that, in previous studies, occurrence has been overestimated due to vague criteria and selected study populations regarding age distribution and low participation.Peer reviewe

Upregulation of Early and Downregulation of Terminal Pathway Complement Genes in Sbcutaneous Adipose Tissue and Adipocytes in Acquired Obesity

Inflammation is an important mediator of obesity-related complications such as the metabolic syndrome but its causes and mechanisms are unknown. As the complement system is a key mediator of inflammation, we studied whether it is activated in acquired obesity in subcutaneous adipose tissue (AT) and isolated adipocytes. We used a special study design of genetically matched controls of lean and heavy groups, rare monozygotic twin pairs discordant for body mass index (BMI) [n = 26, within-pair difference (triangle) in body mass index, BMI >3 kg/m(2)] with as much as 18 kg mean triangle weight. Additionally, 14 BMI-concordant (BMIPeer reviewe

Upregulation of Early and Downregulation of Terminal Pathway Complement Genes in Subcutaneous Adipose Tissue and Adipocytes in Acquired Obesity

Inflammation is an important mediator of obesity-related complications such as the metabolic syndrome but its causes and mechanisms are unknown. As the complement system is a key mediator of inflammation, we studied whether it is activated in acquired obesity in subcutaneous adipose tissue (AT) and isolated adipocytes. We used a special study design of genetically matched controls of lean and heavy groups, rare monozygotic twin pairs discordant for body mass index (BMI) [n = 26, within-pair difference (Δ) in body mass index, BMI >3 kg/m2] with as much as 18 kg mean Δweight. Additionally, 14 BMI-concordant (BMI <3 kg/m2) served as a reference group. The detailed measurements included body composition (DEXA), fat distribution (MRI), glucose, insulin, adipokines, C3a and SC5b-9 levels, and the expression of complement and insulin signaling pathway-related genes in AT and adipocytes. In both AT and isolated adipocytes, the classical and alternative pathway genes were upregulated, and the terminal pathway genes downregulated in the heavier co-twins of the BMI-discordant pairs. The upregulated genes included C1q, C1s, C2, ficolin-1, factor H, receptors for C3a and C5a (C5aR1), and the iC3b receptor (CR3). While the terminal pathway components C5 and C6 were downregulated, its inhibitor clusterin was upregulated. Complement gene upregulation in AT and adipocytes correlated positively with adiposity and hyperinsulinemia and negatively with the expression of insulin signaling-related genes. Plasma C3a, but not SC5b-9, levels were elevated in the heavier co-twins. There were no differences between the co-twins in BMI-concordant pairs. Obesity is associated with increased expression of the early, but not late, complement pathway components and of key receptors. The twins with acquired obesity have therefore an inflated inflammatory activity in the AT. The results suggest that complement is likely involved in orchestrating clearance of apoptotic debris and inflammation in the AT

Genome-wide blood DNA methylation alterations at regulatory elements and heterochromatic regions in monozygotic twins discordant for obesity and liver fat

Abstract Background The current epidemic of obesity and associated diseases calls for swift actions to better understand the mechanisms by which genetics and environmental factors affect metabolic health in humans. Monozygotic (MZ) twin pairs showing discordance for obesity suggest that epigenetic influences represent one such mechanism. We studied genome-wide leukocyte DNA methylation variation in 30 clinically healthy young adult MZ twin pairs discordant for body mass index (BMI; average within-pair BMI difference: 5.4 ± 2.0 kg/m2). Results There were no differentially methylated cytosine-guanine (CpG) sites between the co-twins discordant for BMI. However, stratification of the twin pairs based on the level of liver fat accumulation revealed two epigenetically highly different groups. Significant DNA methylation differences (n = 1,236 CpG sites (CpGs)) between the co-twins were only observed if the heavier co-twins had excessive liver fat (n = 13 twin pairs). This unhealthy pattern of obesity was coupled with insulin resistance and low-grade inflammation. The differentially methylated CpGs included 23 genes known to be associated with obesity, liver fat, type 2 diabetes mellitus (T2DM) and metabolic syndrome, and potential novel metabolic genes. Differentially methylated CpG sites were overrepresented at promoters, insulators, and heterochromatic and repressed regions. Based on predictions by overlapping histone marks, repressed and weakly transcribed sites were significantly more often hypomethylated, whereas sites with strong enhancers and active promoters were hypermethylated. Further, significant clustering of differentially methylated genes in vitamin, amino acid, fatty acid, sulfur, and renin-angiotensin metabolism pathways was observed. Conclusions The methylome in leukocytes is altered in obesity associated with metabolic disturbances, and our findings indicate several novel candidate genes and pathways in obesity and obesity-related complications

Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

BACKGROUND: High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation. METHODS: Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher’s Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network. RESULTS: We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals. CONCLUSIONS: This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Serotonin transporter binding of [123I]ADAM in bulimic women, their healthy twin sisters, and healthy women: a SPET study

<p>Abstract</p> <p>Background</p> <p>Bulimia Nervosa (BN) is believed to be caused by an interaction of genetic and environmental factors. Previous studies support the existence of a bulimia-related endophenotype as well as disturbances in serotonin (5-HT) transmission. We studied serotonin transporter (SERT) binding in BN, and to investigate the possibility of a SERT-related endophenotype for BN, did this in a sample of female twins. We hypothesized clearly reduced SERT binding in BN women as opposed to healthy women, and intermediate SERT binding in unaffected co-twins.</p> <p>Methods</p> <p>We studied 13 female twins with BN (9 with purging and 4 with non-purging BN) and 25 healthy women, including 6 healthy twin sisters of BN patients and 19 women from 10 healthy twin pairs. [¹²³I]ADAM, a selective SERT radioligand for single photon emission tomography (SPET) imaging, was used to assess SERT availability in the midbrain and the thalamus.</p> <p>Results</p> <p>No differences in SERT binding were evident when comparing the BN women, their unaffected co-twins and the healthy controls (p = 0.14). The healthy sisters of the BN patients and the healthy control women had similar SERT binding in both brain regions. In a <it>post hoc </it>subgroup analysis, the purging bulimics had higher SERT binding than the healthy women in the midbrain (p = 0.03), but not in the thalamus.</p> <p>Conclusion</p> <p>Our finding of increased SERT binding in the midbrain in the purging BN women raises the possibility that this subgroup of bulimics might differ in serotonergic function from the non-purging ones. The similarity of the unaffected co-twins and the healthy controls doesn't support our initial assumption of a SERT-related endophenotype for BN. Due to the small sample size, our results need to be interpreted with caution and verified in a larger sample.</p

Association of Lipidome Remodeling in the Adipocyte Membrane with Acquired Obesity in Humans

The authors describe a new approach to studying cellular lipid profiles and propose a compensatory mechanism that may help maintain the normal membrane function of adipocytes in the context of obesity

Use of Genome-Wide Expression Data to Mine the "Gray Zone" of GWA Studies Leads to Novel Candidate Obesity Genes

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