Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine ...and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.
Studies have found a consistent positive association between maternal smoking and non-syndromic orofacial clefts (NSOFC). However, no comprehensive assessment of the association between NSOFC and ...passive smoking has been undertaken. This systematic review and meta-analysis explores the relationship between maternal passive smoking and NSOFC, and compares the associations between passive and active smoking.
Search strategy, inclusion / exclusion criteria, and data extraction from studies reporting maternal passive smoking and NSOFC was implemented without language restrictions. Risks of bias in the identified studies were assessed and this information was used in sensitivity analyses to explain heterogeneity. Meta-analysis and meta-regression of the extracted data were performed. Egger's test was used to test for small study effects. Fourteen eligible articles were identified. Maternal passive smoking exposure was associated with a twofold increase in risk of NSOFC (odds ratio: 2.11, 95% confidence interval: 1.54-2.89); this was apparent for both cleft lip with and without palate (OR: 2.05, 95% CI: 1.27-3.3) and cleft palate (OR: 2.11, 95% CI: 1.23-3.62). There was substantial heterogeneity between studies. In the studies that provided data enabling crude and adjusted odd ratios to be compared, adjustment for potential confounders attenuated the magnitude of association to about a 1.5-fold increase in risk.
Overall, maternal passive smoking exposure results in a 1.5 fold increase in risk of NSOFC, similar to the magnitude of risk reported for active smoking, but there is marked heterogeneity between studies. This heterogeneity is not explained by differences in the distribution of cleft types, adjustment for covariates, broad geographic region, or study bias/quality. This thorough meta-analysis provides further evidence to minimize exposure to environmental tobacco smoke in policy making fora and in health promotion initiatives.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: Vitamin C is an essential nutrient. Sex differences in serum vitamin C concentrations have been observed but are not fully known. Investigation of levels of metabolites may help shed ...light on how dietary and other environmental exposures interact with molecular processes. O-methylascorbate and ascorbic acid 2-sulfate are two metabolites in the vitamin C metabolic pathway. Past research has found genetic factors that influence the levels of these two metabolites. Therefore, we investigated possible effect modification by sex of genetic variant-metabolite associations and characterized the biological function of these interactions. Methods: We included individuals of European descent from the Canadian Longitudinal Study on Aging with available genetic and metabolic data (n = 9004). We used linear mixed models to tests for genome-wide associations with O-methylascorbate and ascorbic acid 2-sulfate, with and without a sex interaction. We also investigated the biological function of the important genetic variant-sex interactions found for each metabolite. Results: Two genome-wide statistically significant ( p value < 5 × 10 −8 ) interaction effects and several suggestive ( p value < 10 –5 ) interaction effects were found. These suggestive interaction effects were mapped to several genes including HSD11B2 , associated with sex hormones, and AGRP , associated with hunger drive. The genes mapped to O-methylascorbate were differently expressed in the testis tissues, and the genes mapped to ascorbic acid 2-sulfate were differently expressed in stomach tissues. Discussion: By understanding the genetic factors that impact metabolites associated with vitamin C, we can better understand its function in disease risk and the mechanisms behind sex differences in vitamin C concentrations.
Abstract
Background
The prolonged effects of disasters on reproductive outcomes among the survivors are less studied, and the findings are inconsistent. We examined the associations of maternal ...exposure to the 2008 Wenchuan earthquake years before conception with adverse birth outcomes.
Methods
We included 73,493 women who delivered in 96 hospitals in 24 provinces and autonomous regions from the 2015/16 China Labor and Delivery Survey. We weighted the multivariable logistic models based on the combination of coarsened exact matching (CEM) weight and survey weight, and performed sex-stratified analysis to test whether associations of maternal earthquake exposure with adverse birth outcomes (Stillbirth, preterm birth PTB, low birthweight LBW, and small for gestational age SGA) varied by sex.
Results
The bivariate models showed that the weighted incidence of each adverse birth outcome was higher in exposed group than unexposed group: stillbirth (2.00% vs. 1.33%), PTB (14.14% vs. 7.32%), LBW (10.82% vs. 5.76%), and SGA (11.32% vs. 9.52%). The multivariable models showed maternal earthquake exposure was only associated significantly with a higher risk of PTB in offspring among all births (adjusted risk ratio aRR(95%CI):1.25(1.06–1.48),
P
= 0.010). The sex-stratified analysis showed the association was significant among male births (aRR (95%CI): 1.40(1.12–1.75),
P
= 0.002),but unsignificant among female births. The sensitivity analysis reported similar findings.
Conclusions
The 2008 Wenchuan earthquake exposure has a long-term effect on PTB. Maternal acute exposure to disasters could be a major monitor for long-term reproductive outcomes. More attention should be paid to the underlining reasons for disaster-related adverse birth outcomes.
Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information into the practice of ...medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and issues of data volume that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.
ObjectivesTo determine the cost-effectiveness of the addition of chromosomal anomalies detectable by non-invasive prenatal screening (NIPS), in a prenatal screening programme targeting common ...aneuploidies.Design, setting and participantsA simulation study was conducted to study the addition of chromosomal anomalies detectable by NIPS (sex chromosome aneuploidies, 22q11.2 deletion syndrome, large deletion/duplication >7 Mb and rare autosomal trisomies) to five basic strategies currently aiming the common trisomies: three strategies currently offered by the public healthcare systems in Canada, whose first-tier test is performed with biochemical markers, and two programmes whose first-tier test consists of NIPS-based methods.Outcome measuresThe total number of cases of chromosomal anomalies detected and the costs related to the consumption of medical services.ResultsThe most effective and the most cost-effective option in almost all prenatal screening strategies is the option that includes all targeted additional conditions. In the strategies where NIPS is used as first-tier testing, the cost per additional case detected by adding all possible additional anomalies to a programme that currently targets only common trisomies is $C25 710 (95% CI $C25 489 to $C25 934) for massively parallel shotgun sequencing and $C57 711 (95% CI $C57 141 to $C58 292) for targeted massively parallel sequencing, respectively. The acceptability curves show that at a willingness-to-pay of $C50 000 per one additional case detected, the expansion of NIPS-based methods for the detection of all possible additional conditions has a 90% probability of being cost-effective.ConclusionFrom an economic perspective, in strategies that use NIPS as a first-tier screening test, expanding the programmes to detect any considered chromosomal anomalies other than the three common trisomies would be cost-effective. However, the potential expansion of prenatal screening programmes also requires consideration of societal issues, including ethical ones.
Previously we have shown that nonsyndromic cleft lip with or without cleft palate (NSCL/P) (1) is strongly associated with SNPs in IRF6 (interferon regulatory factor 6) (2). Here, we use multispecies ...sequence comparisons to identify a common SNP (rs642961, G > A) in a newly identified IRF6 enhancer. The A allele is significantly overtransmitted (P = 1 x 10.sup.-11) in families with NSCL/P, in particular those with cleft lip but not cleft palate. Further, there is a dosage effect of the A allele, with a relative risk for cleft lip of 1.68 for the AG genotype and 2.40 for the AA genotype. EMSA and ChIP assays demonstrate that the risk allele disrupts the binding site of transcription factor AP-2α and expression analysis in the mouse localizes the enhancer activity to craniofacial and limb structures. Our findings place IRF6 and AP-2α in the same developmental pathway and identify a high-frequency variant in a regulatory element contributing substantially to a common, complex disorder.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Persistent infection with certain subtypes of human papillomavirus (HPV) is a necessary cause of cervical cancer. Although two prophylactic vaccines have been licensed in Canada against cancerous ...subtypes of HPV, vaccine uptake has been lower than anticipated. The primary objective of this study was to determine the acceptability of catch-up HPV vaccination to undergraduate university women under the age of 25, by assessing their perceptions of HPV vaccination.
A total of 401 University of Ottawa female undergraduate students participated in a cross-sectional bilingual web-based survey on HPV vaccination.
The prevalence of immunization with at least 1 HPV vaccine dose was 49% in the study population. Although the overall attitude of study participants towards the vaccine was positive, vaccinated respondents had a more favourable attitude towards the vaccine than non-vaccinated respondents. Approximately half of the non-vaccinated respondents were interested in receiving the vaccine at some point in the future. The primary barriers to HPV vaccination identified by non-vaccinated respondents were lack of knowledge about the vaccines, potential vaccine side effects and cost of vaccination. Multivariable analysis comparing non-vaccinated respondents who intended to be vaccinated and those who did not suggests that the former group had a more favourable attitude towards the vaccine and would be influenced by doctor recommendation.
Offering HPV vaccination for women aged 18 to 25 provides an opportunity to address suboptimal vaccination coverage in the population and may reduce health inequities demonstrated by variations in cervical cancer incidence within jurisdictions.
Background
Previous studies showed increases in rates of gastroschisis in Canada in the first decade of the 21st century.
Objective
We sought to examine the epidemiologic characteristics of ...gastroschisis in Canada in recent years.
Methods
We conducted a retrospective population‐based cohort study of all livebirths and stillbirths delivered in Canada (excluding Quebec) from 2006 to 2017, with information obtained from the Canadian Institute for Health Information. Gastroschisis rates by maternal age, region of residence, and maternal and infant characteristics were quantified using prevalence rate ratios (RR) and 95% confidence intervals (CI). Log‐binomial regression was used to quantify the associations between risk factors and gastroschisis.
Results
There were 1314 gastroschisis cases among 3 364 116 births. The prevalence rate was 3.7 per 10 000 total births in 2006 and 3.4 per 10 000 total births in 2017, with substantial annual variation in rates. The proportion of mothers aged 20–24 years decreased from 16.5% in 2006 to 11.3% in 2017, while the proportion of mothers aged <20 years halved from 4.8% to 2.3%. The prevalence of gastroschisis at birth remained unchanged among mothers aged <20, 20–24 and 30–49 years but increased among mothers aged 25–29 years. The age‐adjusted prevalence rate of gastroschisis increased across the period (for 2016–2017 versus 2006–2007 rate ratio RR 1.28, 95% CI 1.05, 1.56), and there was substantial regional variation. Risk factors included problematic use of substances (RR 2.61, 95% CI 2.01, 3.39) and hypothyroidism (RR 2.76, 95% CI 1.56, 4.88). There was a North‐to‐South difference in gastroschisis prevalence (adjusted RR Far North compared with South 1.54, 95% CI 1.11, 2.15).
Conclusion
Gastroschisis birth prevalence rates in Canada have stabilised in recent years compared with the increase documented previously. The substantial geographic variation and North‐to‐South difference in gastroschisis prevalence may indicate variation in socio‐economic status, lifestyle and nutritional patterns.
Abstract Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of ...medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence, the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association (STREGA) studies initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy–Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.
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