共查询到20条相似文献，搜索用时 15 毫秒
1.
Boyoung Park So Young Kim Ji-Yeon Shin Robert W. Sanson-Fisher Dong Wook Shin Juhee Cho Jong Hyock Park 《PloS one》2013,8(4)
Purpose
To describe the prevalence of suicidal ideation and suicide attempts in family caregivers (FCs) of patients with cancer and to identify the factors associated with suicidal ideation and suicide attempts in FCs with anxiety or depression.Methods
A national, multicenter survey administered to 897 FCs asked questions concerning suicidal ideation and suicide attempts during the previous year and assessed anxiety, depression, socio–demographic factors, caregiving burden, patient factors, and quality of life (QOL).Results
A total of 17.7% FCs reported suicidal ideation, and 2.8% had attempted suicide during the previous year. Among FCs with anxiety, 31.9% had suicidal ideation and 4.7% attempted suicide; the corresponding values for FCs with depression were 20.4% and 3.3%, respectively. Compared with FCs without anxiety and depression, FCs with anxiety or depression showed a higher adjusted odds ratios (aOR) for suicidal ideation (aOR = 4.07 and 1.93, respectively) and attempts (OR = 3.00 and 2.43, respectively). Among FCs with anxiety or depression, being female, unmarried, unemployed during caregiving, and having a low QOL were associated with increased odds of suicidal ideation. FCs with anxiety who became unemployed during caregiving constituted a high-risk group for suicide. Being unmarried and having a low QOL with respect to financial matters were associated with increased suicide attempts among FCs with depression.Conclusion
FCs with anxiety or depression were at high risk of suicide. Interventions to enhance social support and to improve perceived QOL may help prevent suicide and manage suicidal ideation in FCs with anxiety or depression. 相似文献2.
Background
There has been no study that has allowed clear conclusions about the impact of suicide-related or mental health consultation-related internet use.Aim
To investigate the impacts of suicide-related or mental health consultation-related internet use.Methods
We conducted prospective observational longitudinal study with data collection at baseline screening (T0), 1 week after T0 (T1) and 7 weeks after T0 (T2). Participants with a stratified random sampling from 744,806 internet users were 20–49 years of age who employed the internet for suicide-related or mental health consultation-related reasons and internet users who did not. The main outcome was suicidal ideation. Secondary outcome measures comprised hopelessness, depression/anxiety, and loneliness.Results
The internet users who had employed the internet for suicide-related or mental health consultation-related reasons at T0 (n = 2813), compared with those who had not (n = 2682), showed a significant increase in suicidal ideation (β = 0.38, 95%CI: 0.20–0.55) and depression/anxiety (β = 0.37, 95%CI: 0.12–0.61) from T1 to T2. Those who disclosed their own suicidal ideation and browsed for information about suicide methods on the web showed increased suicidal ideation (β = 0.55, 95%CI: 0.23–0.88; β = 0.45, 95% CI: 0.26–0.63, respectively). Although mental health consultation with an anonymous other online did not increase suicidal ideation, increased depression/anxiety was observed (β = 0.34, 95%CI: −0.03–0.71).Conclusions
An increased suicidal ideation was observed in the young and middle-aged who employed the internet for suicide-related or mental health consultation-related reasons. Mental health consultation via the internet was not useful, but those who did so showed worsened depression/anxiety. 相似文献3.
Yuko Kitagawa Shinji Shimodera Fumiharu Togo Yuji Okazaki Atsushi Nishida Tsukasa Sasaki 《PloS one》2014,9(9)
Purpose
Being bullied is associated with the manifestation of suicidal feelings, which sharply increase in middle(-late) adolescence. Whether or not bullied middle(-late) adolescents with suicidal feelings seek help is therefore a critical issue, given that help-seeking plays a key role in the prevention of suicide. The aim of the present study is to investigate the effects of bullying, suicidal feelings and the interaction between these two factors on help-seeking behavior in adolescents.Methods
Japanese middle(-late) adolescents (aged 15–18 years; n = 9484) were studied using self-report questionnaires. The rate of adolescents who actually sought help was examined for bullying status and suicidal feelings.Results
The rate of adolescents who sought help was significantly higher when they were bullied (p<0.001) and also when they had mild suicidal feelings (p<0.001), but not when they displayed serious suicidal feelings. In the case of adolescents who were bullied, however, having suicidal feelings significantly decreased the rate of help-seeking (OR = 0.47, p<0.05 and OR = 0.32, p = 0.002 for having mild and serious suicidal feelings, respectively). The decrease was remarkable when suicidal feelings were serious. Specifically, the decrease was significant in seeking help from peers and family members, who are the most frequent source of the help for adolescents, when they had serious suicidal feelings (OR = 0.21, p<0.01 and OR = 0.13, p<0.001, respectively).Conclusions
Suicidal feelings may interfere with help-seeking behavior, which could be critical in suicide prevention in bullied middle(-late) adolescents. 相似文献4.
Objective
Increasing rates of disability pension (DP) have been observed among young adults. We studied specific psychiatric DP diagnoses and subsequent risk of suicidal behaviour in a series of three cohorts of young adult in Sweden.Method
In a nationwide register study, we included all young adults who in 1995, 2000, and 2005, respectively, were 19–23 years old and lived in Sweden (n≈500,000 per cohort). Rates of DP and specific psychiatric DP diagnoses were recorded in each cohort. Hazard ratios (HRs) and 95% confidence intervals (CIs) for suicidal behaviour during the following five years, with the corresponding age group as reference, were calculated by Cox proportional hazard regression, adjusted for demographic variables and previous own and parental suicidal behaviour.Results
The overall proportion with DP in this age group increased from 0.92% in 1995 to 2.29% in 2005, with particularly large increases in psychiatric diagnoses such as hyperkinetic disorders, pervasive developmental disorders, and depression/anxiety. The overall proportion of young disability pensioners attempting suicide during the five-year follow-up increased from 2.21% in the 1995 cohort to 3.81% in the 2005 cohort. Within most psychiatric DP diagnoses, the risk of attempted suicide did not change significantly over time, whereas suicide attempts increased in the reference group. Accordingly, the HRs for suicide attempt decreased in some psychiatric DP diagnoses. The highest adjusted HRs were observed for depression/anxiety (16.41; CI: 9.06 to 29.74) and schizophrenia (9.37; 6.13 to 14.31) in the 1995 cohort. The rate of suicide among young disability pensioners during follow-up ranged from 0.19% in 1995 to 0.37% in 2005, mainly occurring in individuals with psychiatric diagnoses.Conclusion
Suicidal behaviour has become more prevalent among young disability pensioners, which co-occurred with an increased tendency to grant DP in psychiatric diagnoses with a known high risk of suicidal behaviour. Preventive measures are warranted. 相似文献5.
Purpose
A recent large genome-wide association study (GWAS) identified multiple variants associated with primary angle-closure glaucoma (PACG). The present study investigated the role of these variants in two cohorts with PACG recruited from Australia and Nepal.Method
Patients with PACG and appropriate controls were recruited from eye clinics in Australia (n = 232 cases and n = 288 controls) and Nepal (n = 106 cases and 204 controls). Single nucleotide polymorphisms (SNPs) rs3753841 (COL11A1), rs1015213 (located between PCMTD1 and ST18), rs11024102 (PLEKHA7), and rs3788317 (TXNRD2) were selected and genotyped on the Sequenom. Analyses were conducted using PLINK and METAL.Results
After adjustment for age and sex, SNP rs3753841 was found to be significantly associated with PACG in the Australian cohort (p = 0.017; OR = 1.34). SNPs rs1015213 (p = 0.014; OR 2.35) and rs11024102 (p = 0.039; OR 1.43) were significantly associated with the disease development in the Nepalese cohort. None of these SNPs survived Bonferroni correction (p = 0.05/4 = 0.013). However, in the combined analysis, of both cohorts, rs3753841 and rs1015213 showed significant association with p-values of 0.009 and 0.004, respectively both surviving Bonferroni correction. SNP rs11024102 showed suggestive association with PACG (p-value 0.035) and no association was found with rs3788317.Conclusion
The present results support the initial GWAS findings, and confirm the SNP’s contribution to PACG. This is the first study to investigate these loci in both Australian Caucasian and Nepalese populations. 相似文献6.
Joanna E. Cobb Darren Plant Edward Flynn Meriem Tadjeddine Philippe Dieudé Fran?ois Cornélis Lisbeth ?rlestig Solbritt Rantap?? Dahlqvist George Goulielmos Dimitrios T. Boumpas Prodromos Sidiropoulos Sophine B. Krintel Lykke M. ?rnbjerg Merete L. Hetland Lars Klareskog Thomas Haeupl Andrew Filer Christopher D. Buckley Karim Raza Torsten Witte Reinhold E. Schmidt Oliver FitzGerald Douglas Veale Stephen Eyre Jane Worthington 《PloS one》2013,8(6)
Objectives
Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA.Methods
A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data.Results
Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4×10−9).Conclusions
This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase) with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene. 相似文献7.
Fox AA Pretorius M Liu KY Collard CD Perry TE Shernan SK De Jager PL Hafler DA Herman DS DePalma SR Roden DM Muehlschlegel JD Donahue BS Darbar D Seidman JG Body SC Seidman CE 《PloS one》2011,6(9):e24593
Background
Postoperative ventricular dysfunction (VnD) occurs in 9–20% of coronary artery bypass graft (CABG) surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery.Methods
A genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for ≥2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed.Results
Over 100 SNPs were associated with VnD (P<10−4), with one SNP (rs17691914) encoded at 3p22.3 reaching genome-wide significance (Padditive model = 2.14×10−8). Meta-analysis of validation and replication study data for 17 SNPs identified three SNPs associated with increased risk for developing postoperative VnD after adjusting for clinical risk factors. These SNPs are located at 3p22.3 (rs17691914, ORadditive model = 2.01, P = 0.0002), 3p14.2 (rs17061085, ORadditive model = 1.70, P = 0.0001) and 11q23.2 (rs12279572, ORrecessive model = 2.19, P = 0.001).Conclusions
No SNPs were consistently associated with strong risk (ORadditive model>2.1) of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted. 相似文献8.
MF Hughes O Saarela J Stritzke F Kee K Silander N Klopp J Kontto J Karvanen C Willenborg V Salomaa J Virtamo P Amouyel D Arveiler J Ferrières PG Wiklund J Baumert B Thorand P Diemert DA Trégouët C Hengstenberg A Peters A Evans W Koenig J Erdmann NJ Samani K Kuulasmaa H Schunkert 《PloS one》2012,7(7):e40922
Background
More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.Methods
Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5–18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.Results
Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50–59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.Conclusions
Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men. 相似文献9.
Objective
Compared to other eating disorders, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an eating disorders (ED).Method
Case-control study in a cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity.Results
AN patients were more likely to have made a serious attempt (OR = 3.4, 95% CI 1.4–7.9), with a higher expectation of dying (OR = 3.7,95% CI 1.1–13.5), and an increased risk of severity (OR = 3.4,95% CI 1.2–9.6). BN patients did not differ from the control group. Clinical markers of the severity of ED were associated with the seriousness of the attempt.Conclusion
There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Higher completed suicide rates in AN may be partially explained by AN patients'' higher desire to die and their more severe and lethal attempts. 相似文献10.
Background
Two treatments for smoking cessation—varenicline and bupropion—carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown.Methodology
From the FDA''s Adverse Event Reporting System (AERS) database from 1998 through September 2010 we selected domestic, serious case reports for varenicline (n = 9,575), bupropion for smoking cessation (n = 1,751), and nicotine replacement products (n = 1,917). A composite endpoint of suicidal/self-injurious behavior or depression was defined as a case with one or more Preferred Terms in Standardized MedDRA Query (SMQ) for those adverse effects. The main outcome measure was the ratio of reported suicide/self-injury or depression cases for each drug compared to all other serious events for that drug.Results
Overall we identified 3,249 reported cases of suicidal/self-injurious behavior or depression, 2,925 (90%) for varenicline, 229 (7%) for bupropion, and 95 (3%) for nicotine replacement. Compared to nicotine replacement, the disproportionality results (OR (95% CI)) were varenicline 8.4 (6.8–10.4), and bupropion 2.9 (2.3–3.7). The disproportionality persisted after excluding reports indicating concomitant therapy with any of 58 drugs with suicidal behavior warnings or precautions in the prescribing information. An additional antibiotic comparison group showed that adverse event reports of suicidal/self-injurious behavior or depression were otherwise rare in a healthy population receiving short-term drug treatment.Conclusions
Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation. 相似文献11.
Background
Suicide has been linked to intense negative affect. However, little is known about the range of affects experienced by suicidal persons, or the separate effects of affect valence and intensity. We examine a novel self-report scale, the 17-item Affective Intensity Rating Scale (AIRS), and its relation to suicidality in a high-risk sample.Methodology/Principal Findings
Patients presenting with suicidality were recruited from the Emergency Department in a large urban hospital, and completed a battery of assessments there. Structure of the AIRS was assessed using Maximum Likelihood Factor Analysis with Oblimin rotation. Convergent and divergent validity were assessed by regressing AIRS subscales against Brief Symptom Inventory subscales. Relation to suicidality was assessed by regression of suicide attempt status against scale and subscale scores, and individual items and two-way item interactions, along with significant clinical and demographic factors. 176 subjects were included in analyses. Three reliable subscales were identified within the AIRS measure: positive feelings towards self, negative feelings towards self, and negative feelings towards other. Only individual AIRS items associated significantly with suicide attempt status; strong ‘feelings of love’ associated positively with actual suicide attempt, while ‘feelings of calm’ and ‘positive feelings towards self’ associated negatively. Interaction analyses suggest ‘calm’ moderates the association of ‘love’ with suicide attempt.Conclusions/Significance
Factor analysis of the AIRS is consistent with a circumplex model of affect. Affective dimensions did not predict suicidal behavior, but intense feelings of love, particularly in the absence of protective feelings of calm or positive self-view associated with current attempt. 相似文献12.
Yu X Koczan D Sulonen AM Akkad DA Kroner A Comabella M Costa G Corongiu D Goertsches R Camina-Tato M Thiesen HJ Nyland HI Mørk SJ Montalban X Rieckmann P Marrosu MG Myhr KM Epplen JT Saarela J Ibrahim SM 《PloS one》2008,3(2):e1530
Background
Mitochondrial DNA (mtDNA) polymorphism is a possible factor contributing to the maternal parent-of-origin effect in multiple sclerosis (MS) susceptibility.Methods and Findings
In order to investigate the role of mtDNA variations in MS, we investigated six European MS case-control cohorts comprising >5,000 individuals. Three well matched cohorts were genotyped with seven common, potentially functional mtDNA single nucleotide polymorphisms (SNPs). A SNP, nt13708 G/A, was significantly associated with MS susceptibility in all three cohorts. The nt13708A allele was associated with an increased risk of MS (OR = 1.71, 95% CI 1.28–2.26, P = 0.0002). Subsequent sequencing of the mtDNA of 50 individuals revealed that the nt13708 itself, rather than SNPs linked to it, was responsible for the association. However, the association of nt13708 G/A with MS was not significant in MS cohorts which were not well case-control matched, indicating that the significance of association was affected by the population structure of controls.Conclusions
Taken together, our finding identified the nt13708A variant as a susceptibility allele to MS, which could contribute to defining the role of the mitochondrial genome in MS pathogenesis. 相似文献13.
Tatiana Falcone Vincent Fazio Catherine Lee Barry Simon Kathleen Franco Nicola Marchi Damir Janigro 《PloS one》2010,5(6)
Background
Studies have shown that patients suffering from depression or schizophrenia often have immunological alterations that can be detected in the blood. Others reported a possible link between inflammation, a microgliosis and the blood-brain barrier (BBB) in suicidal patients. Serum S100B is a marker of BBB function commonly used to study cerebrovascular wall function.Methods
We measured levels of S100B in serum of 40 adolescents with acute psychosis, 24 adolescents with mood disorders and 20 healthy controls. Patients were diagnosed according to DSM-IV TR criteria. We evaluated suicidal ideation using the suicidality subscale of the Brief Psychiatric Rating Scale for Children (BPRS-C).Results
Serum S100B levels were significantly higher (p<0.05) and correlated to severity of suicidal ideation in patients with psychosis or mood disorders, independent of psychiatric diagnosis. Patients with a BPRS-C suicidality subscores of 1–4 (low suicidality) had mean serum S100B values +/− SEM of 0.152+/−0.020 ng/mL (n = 34) compared to those with BPRS-C suicidality subscores of 5–7 (high suicidality) with a mean of 0.354+/−0.044 ng/mL (n = 30). This difference was statistically significant (p<0.05).Conclusion
Our data support the use of S100B as an adjunctive biomarker to assess suicidal risk in patients with mood disorders or schizophrenia. 相似文献14.
Objectives
The objective of this study was to examine, first, the relationship of having a rural vs. urban background with suicidal ideation in Chinese college students, and second, whether a potential relationship was mediated by depression.Methods
A survey was conducted among 1,145 undergraduate students at a university in China. Suicidal ideation and depressive symptoms were measured by the revised Hopkins’ Symptom checklist (SCL-90-R). Associations between rural vs. urban background, depression and suicidal ideation were estimated by multivariable linear regression-based β coefficients, logistic regression-based odds ratios (ORs), and corresponding 95% confidence intervals (CIs). The magnitude of indirect effect and bias-corrected 95% CIs were obtained through bootstrap techniques.Results
Rural background was positively associated with depression, which was in turn associated with suicidal ideation. The OR for rural status and suicidal ideation equaled 2.15 (95% CI = 1.36–3.41). This OR was slightly, though significantly (p<0.05) attenuated by additional adjustment for depressive symptoms (OR = 1.99, 95% CI = 1.15–3.44).Conclusion
Having a rural background is a determinant of suicidal ideation in Chinese college students. Depression may only marginally mediate this association. 相似文献15.
Paternoster L Evans DM Nohr EA Holst C Gaborieau V Brennan P Gjesing AP Grarup N Witte DR Jørgensen T Linneberg A Lauritzen T Sandbaek A Hansen T Pedersen O Elliott KS Kemp JP St Pourcain B McMahon G Zelenika D Hager J Lathrop M Timpson NJ Smith GD Sørensen TI 《PloS one》2011,6(9):e24303
Background
Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ∼1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations.Methodology/Principal Findings
From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ∼212,000 individuals). We followed up novel (at the time of the study) association signals (p<0.001) from the discovery cohort in a genome-wide study of 5,846 Europeans, before attempting to replicate the most strongly associated 28 SNPs in an independent sample of Danish individuals (n = 20,917) and a population-based cohort of 15-year-old British adolescents (n = 2,418). Our discovery analysis identified SNPs at three loci known to be associated with BMI with genome-wide confidence (P<5×10−8; FTO, MC4R and FAIM2). We also found strong evidence of association at the known TMEM18, GNPDA2, SEC16B, TFAP2B, SH2B1 and KCTD15 loci (p<0.001), and nominal association (p<0.05) at a further 8 loci known to be associated with BMI. However, meta-analyses of our discovery and replication cohorts identified no novel associations.Significance
Our results indicate that the detectable genetic variation associated with extreme overweight is very similar to that previously found for general BMI. This suggests that population-based study designs with enriched sampling of individuals with the extreme phenotype may be an efficient method for identifying common variants that influence quantitative traits and a valid alternative to genotyping all individuals in large population-based studies, which may require tens of thousands of subjects to achieve similar power. 相似文献16.
Shinji Yoshida Katsunori Ikari Takefumi Furuya Yoshiaki Toyama Atsuo Taniguchi Hisashi Yamanaka Shigeki Momohara 《PloS one》2014,9(8)
Introduction
Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA.Methods
DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model.Results
The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95% CI] = 2.53 [1.29–4.95], P = 0.0067). No association was found for the other SNPs.Conclusions
Our results indicate that an OPG allele is associated with increased risk for hip fracture in Japanese patients with RA. 相似文献17.
《PloS one》2012,7(9)
Rationale
Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies.Objectives
To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations.Methods
The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5x10−8) and three variants reported as suggestive (P<5×10−7). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever.Main Results
We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4×10−9). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P Stage1+Stage2 = 1.1x10−9), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P Stage1+Stage2 = 1.1x10−8), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status.Conclusions
Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma. 相似文献18.
Dominique S. Michaud Afshan Siddiq David G. Cox Danielle M. Backes Federico C. F. Calboli Michael E. Sughrue J. Michael Gaziano Jing Ma Meir Stampfer Shelley S. Tworoger David J. Hunter Carlos A. Camargo Jr Andrew T. Parsa 《PloS one》2013,8(4)
Background and Aims
The immune system is likely to play a key role in the etiology of gliomas. Genetic polymorphisms in the mannose-binding lectin gene, a key activator in the lectin complement pathway, have been associated with risk of several cancers.Methods
To examine the role of the lectin complement pathway, we combined data from prospectively collected cohorts with available DNA specimens. Using a nested case-control design, we genotyped 85 single nucleotide polymorphisms (SNPs) in 9 genes in the lectin complement pathway and 3 additional SNPs in MBL2 were tested post hoc). Initial SNPs were selected using tagging SNPs for haplotypes; the second group of SNPs for MBL2 was selected based on functional SNPs related to phenotype. Associations were examined using logistic regression analysis. All statistical tests were two-sided. Nominal p-values are presented and are not corrected for multiple comparisons.Results
A total of 143 glioma cases and 419 controls were available for this analysis. Statistically significant associations were observed for two SNPs in the mannose-binding lectin 2 (ML2) gene and risk of glioma (rs1982266 and rs1800450, test for trend p = 0.003 and p = 0.04, respectively, using the additive model). One of these SNPs, rs1800450, was associated with a 58% increase in glioma risk among those carrying one or two mutated alleles (odds ratio = 1.58, 95% confidence interval = 0.99–2.54), compared to those homozygous for the wild type allele.Conclusions
Overall, our findings suggest that MBL may play a role in the etiology of glioma. Future studies are needed to confirm these findings which may be due to chance, and if reproduced, to determine mechanisms that link glioma pathogenesis with the MBL complement pathway. 相似文献19.
20.
James Whitehorn Tran Nguyen Bich Chau Nguyen Minh Nguyet Duong Thi Hue Kien Nguyen Than Ha Quyen Dinh The Trung Junxiong Pang Bridget Wills Nguyen Van Vinh Chau Jeremy Farrar Martin L. Hibberd Chiea Chuen Khor Cameron P. Simmons 《PloS one》2013,8(3)