Abstract
BACKGROUND
Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but ...with substantial clinical heterogeneity.
OBJECTIVE AND RATIONALE
We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS.
SEARCH METHODS
We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle–Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel–Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis.
OUTCOMES
We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17–4.90) and T2DM (OR = 2.87, 95% CI: 1.44–5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for diagnosing diabetes. The ethnicity-related difference retained its significance for Asia and Europe in BMI-matched subgroups. Clear contributors to heterogeneity did not emerge in meta-regression.
WIDER IMPLICATIONS
Our findings underscore the importance of PCOS as a cause of dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance of ethnicity and obesity and emphasize the need for accurate diagnostic methods for diabetes.
PROSPERO REGISTRATION NUMBER
CRD42017056524.
Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder of complex genetic etiology. Previous genome-wide surveys have revealed a greater burden of large, rare copy number variations ...(CNVs) in SCZ cases and identified multiple rare recurrent CNVs that increase risk of SCZ although with incomplete penetrance and pleiotropic effects. Identification of additional recurrent CNVs and biological pathways enriched for SCZ CNVs requires greater sample sizes. We conducted a genome-wide survey for CNVs associated with SCZ using a Swedish national sample (4719 cases and 5917 controls). High-confidence CNV calls were generated using genotyping array intensity data, and their effect on risk of SCZ was measured. Our data confirm increased burden of large, rare CNVs in SCZ cases as well as significant associations for recurrent 16p11.2 duplications, 22q11.2 deletions and 3q29 deletions. We report a novel association for 17q12 duplications (odds ratio=4.16, P=0.018), previously associated with autism and mental retardation but not SCZ. Intriguingly, gene set association analyses implicate biological pathways previously associated with SCZ through common variation and exome sequencing (calcium channel signaling and binding partners of the fragile X mental retardation protein). We found significantly increased burden of the largest CNVs (>500 kb) in genes present in the postsynaptic density, in genomic regions implicated via SCZ genome-wide association studies and in gene products localized to mitochondria and cytoplasm. Our findings suggest that multiple lines of genomic inquiry--genome-wide screens for CNVs, common variation and exonic variation--are converging on similar sets of pathways and/or genes.
Summary
Introduction
Women with polycystic ovary syndrome (PCOS) have increased risk of metabolic syndrome. The relative contribution of clinical, demographic or biochemical factors to metabolic ...syndrome in PCOS is not known. A literature search was conducted in MEDLINE, CINAHL, EMBASE and clinical trial registries. Of 4530 studies reviewed, 59 were included in the systematic review and 27 in the meta‐analysis and meta‐regression. In good and fair quality studies, women with PCOS had an overall increased prevalence of metabolic syndrome (odds ratio, OR 3.35, 95% confidence interval, CI 2.44, 4.59). Increased prevalence of metabolic syndrome occurred in overweight or obese women with PCOS (OR 1.88, 95% 1.16, 3.04) but not in lean women (OR 1.45, 95% CI 0.35, 6.12). In meta‐regression analyses, the markers of metabolic syndrome diagnostic criteria (waist circumference, high‐density lipoprotein cholesterol, triglyceride, blood pressure), BMI, glucose tolerance (2‐hr oral glucose tolerance test) and surrogate markers of insulin resistance (HOMA‐IR) but not markers of reproductive dysfunction (sex hormone binding globulin, testosterone, PCOS phenotypes) contributed significantly to the heterogeneity in the prevalence of metabolic syndrome. Women with PCOS have increased risk of metabolic syndrome which was associated with obesity and metabolic features but not with indices of hyperandrogenism.
We report a new geometric maser distance estimate to the active galaxy NGC 4258. The data for the new model are maser line-of-sight (LOS) velocities and sky positions from 18 epochs of very long ...baseline interferometry observations, and LOS accelerations measured from a 10 yr monitoring program of the 22 GHz maser emission of NGC 4258. The new model includes both disk warping and confocal elliptical maser orbits with differential precession. The distance to NGC 4258 is 7.60 + or - 0.17 + or - 0.15 Mpc, a 3% uncertainty including formal fitting and systematic terms. The resulting Hubble constant, based on the use of the Cepheid variables in NGC 4258 to recalibrate the Cepheid distance scale, is H sub(0) = 72.0 + or - 3.0 km s super(-1) Mpc super(-1).
We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed ...with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10
) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h
=0.35; BD II SNP-h
=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
Summary
While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to ...assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone‐binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment‐insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total‐cholesterol and low‐density lipoprotein‐cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.
The Galactic center supermassive black hole Sagittarius A* (Sgr A*) is one of the most promising targets to study the dynamics of black hole accretion and outflow via direct imaging with very long ...baseline interferometry (VLBI). At 3.5 mm (86 GHz), the emission from Sgr A* is resolvable with the Global Millimeter VLBI Array (GMVA). We present the first observations of Sgr A* with the phased Atacama Large Millimeter/submillimeter Array (ALMA) joining the GMVA. Our observations achieve an angular resolution of ∼87 as, improving upon previous experiments by a factor of two. We reconstruct a first image of the unscattered source structure of Sgr A* at 3.5 mm, mitigating the effects of interstellar scattering. The unscattered source has a major-axis size of 120 34 as (12 3.4 Schwarzschild radii) and a symmetrical morphology (axial ratio of ), which is further supported by closure phases consistent with zero within 3 . We show that multiple disk-dominated models of Sgr A* match our observational constraints, while the two jet-dominated models considered are constrained to small viewing angles. Our long-baseline detections to ALMA also provide new constraints on the scattering of Sgr A*, and we show that refractive scattering effects are likely to be weak for images of Sgr A* at 1.3 mm with the Event Horizon Telescope. Our results provide the most stringent constraints to date for the intrinsic morphology and refractive scattering of Sgr A*, demonstrating the exceptional contribution of ALMA to millimeter VLBI.
According to the Global Burden of Disease Study, between 1990 and 2013, global cardiovascular mortality increased by 55% as a result of aging and by 25% as a result of population growth. A 39% ...decrease in age-specific death rates resulted in a 41% increase in cardiovascular mortality.
Globally, deaths from cardiovascular and circulatory diseases are increasing.
1
This increase represents the combined effect of population growth, the aging of populations, and epidemiologic changes in cardiovascular disease. It is important to disentangle these drivers of the observed trends in global mortality for a number of reasons. First, regional and national investments in cardiovascular health can target only the epidemiologic causes of cardiovascular disease. Second, understanding the roles and relative magnitude of these demographic and epidemiologic trends is important in planning for the health care system and in developing policy. Third, the effects of the aging and growth of the . . .
We have conducted a genotyping study using a custom Illumina Infinium HD genotyping array, the ImmunoChip, in a new UK sample of 1218 bipolar disorder (BD) cases and 2913 controls that have not been ...used in any studies previously reported independently or in meta-analyses. The ImmunoChip was designed before the publication of the Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder Working Group (PGC-BD) meta-analysis data. As such 3106 single-nucleotide polymorphisms (SNPs) with a P-value <1 × 10(-3) from the BD meta-analysis by Ferreira et al. were genotyped. We report support for two of the three most strongly associated chromosomal regions in the Ferreira study, CACNA1C (rs1006737, P=4.09 × 10(-4)) and 15q14 (rs2172835, P=0.043) but not ANK3 (rs10994336, P=0.912). We have combined our ImmunoChip data (569 quasi-independent SNPs from the 3016 SNPs genotyped) with the recently published PGC-BD meta-analysis data, using either the PGC-BD combined discovery and replication data where available or just the discovery data where the SNP was not typed in a replication sample in PGC-BD. Our data provide support for two regions, at ODZ4 and CACNA1C, with prior evidence for genome-wide significant (GWS) association in PGC-BD meta-analysis. In addition, the combined analysis shows two novel GWS associations. First, rs7296288 (P=8.97 × 10(-9), odds ratio (OR)=0.9), an intergenic polymorphism on chromosome 12 located between RHEBL1 and DHH. Second, rs3818253 (P=3.88 × 10(-8), OR=1.16), an intronic SNP on chromosome 20q11.2 in the gene TRPC4AP, which lies in a high linkage disequilibrium region along with the genes GSS and MYH7B.
BACKGROUND Polycystic ovary syndrome (PCOS) is closely associated with obesity but the prevalence of obesity varies between published studies. The objective of this research was to describe the ...prevalence of overweight, obesity and central obesity in women with and without PCOS and to assess the confounding effect of ethnicity, geographic regions and the diagnostic criteria of PCOS on the prevalence. METHODS MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting the prevalence of overweight, obesity or central obesity in women with and without PCOS. Data were presented as prevalence (%) and risk ratio (RR) 95% confidence interval (CI). Random-effect models were used to calculate pooled RR. RESULTS This systematic review included 106 studies while the meta-analysis included 35 studies (15129 women). Women with PCOS had increased prevalence of overweight RR (95% CI): 1.95 (1.52, 2.50), obesity 2.77 (1.88, 4.10) and central obesity 1.73 (1.31, 2.30) compared with women without PCOS. The Caucasian women with PCOS had a greater increase in obesity prevalence than the Asian women with PCOS compared with women without PCOS 10.79 (5.36, 21.70) versus 2.31 (1.33, 4.00), P < 0.001 between subgroups). CONCLUSIONS Women with PCOS had a greater risk of overweight, obesity and central obesity. Although our findings support a positive association between obesity and PCOS, our conclusions are limited by the significant heterogeneity between studies and further studies are now required to determine the source of this heterogeneity. Clinical management of PCOS should include the prevention and management of overweight and obesity.
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