Paternal age and risk for schizophrenia

BackgroundPreviously reported associations between advancing paternal age and schizophrenia could be due to an increase in paternal germ cell mutations or be confounded by heritable personality traits associated with schizophrenia that result in delayed parenthood.AimsTo investigate this association while adjusting for personality traits related to poor social integration in the subjects.MethodA cohort of 50 087 adolescent males was followed up by record linkage to determine hospital admissions for schizophrenia between 1970 and 1996.ResultsAdvancing paternal age was associated with an increased risk of developing schizophrenia in a ‘dose-dependent’ manner. The adjusted odds ratio for each 10-year increase in paternal age was 1.3 (95% Cl 1.0–1.5; P=0.015).ConclusionsAdvancing paternal age is an independent risk factor for schizophrenia. Adjusting for social integration in subjects made little difference to this association, consistent with the hypothesis that advancing paternal age may increase liability to schizophrenia owing to accumulating germ cell mutations.

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Paternal smoking is associated with an increased risk of pregnancy loss in a dose-dependent manner: a systematic review and meta-analysis

F&S Reviews ◽

10.1016/j.xfnr.2021.06.001 ◽

2021 ◽

Author(s):

Nadia A. du Fossé ◽

Marie-Louise P. van der Hoorn ◽

Nina H. Buisman ◽

Jan M.M. van Lith ◽

S askia le Cessie ◽

...

Keyword(s):

Systematic Review ◽

Pregnancy Loss ◽

Meta Analysis ◽

Dependent Manner ◽

Increased Risk ◽

Dose Dependent ◽

Paternal Smoking

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GFI1 Is a Tumor Suppressor in Myeloid Progenitors

Blood ◽

10.1182/blood.v112.11.2942.2942 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2942-2942

Author(s):

Aditya Chaubey ◽

Shane Hormon ◽

Chinavenmeni S. Velu ◽

Tristan Bourdeau ◽

Jinfang Zhu ◽

...

Keyword(s):

Dna Sequences ◽

Myeloid Leukemia ◽

Dependent Manner ◽

Loss Of Function ◽

Increased Risk ◽

Myeloid Leukemias ◽

Dose Dependent ◽

Anterior Posterior

Abstract In severe congenital neutropenia (SCN) patients and mice with Growth factor independent-1 (Gfi1) loss of function, arrested progenitors are suspended in a hyperproliferative state while terminal granulpoiesis is blocked. SCN patients are at increased risk for the development of acute myeloid leukemia. We demonstrate that Gfi1 directly targets HoxA9, Pbx1 and Meis1 during normal myelopoiesis. Gfi1−/− progenitors exhibit elevated levels of HoxA9, Pbx1 and Meis1, exaggerated HoxA9-Pbx1-Meis1 activity, and increased persistence in vivo and in vitro. Limiting HoxA9 alleles corrects, in a dose dependent manner, in vivo and in vitro phenotypes observed with loss of Gfi1. Moreover, in a manner conserved in Drosophila anterior/posterior patterning, we demonstrate that these factors can compete for occupancy of DNA sequences encoding composite Gfi1-HoxA9-Pbx1-Meis1 binding sites. Finally, the expression of Gfi1 and HoxA9 are inverse and stratify human myeloid leukemias, suggesting a role for HoxA9- Gfi1 antagonism in human AML. In agreement with this, a myeloproliferative disorder progresses into a rapid, lethal and transplantable myeloid leukemia in a Gfi1−/− setting. We conclude that the lifespan and oncogenic transformation of hematopoietic progenitor cells is regulated through a conserved competition between Gfi1 and HoxA9-Pbx1-Meis1.

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Premorbid body mass and mortality in patients with hepatocellular cancer: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.477 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 477-477 ◽

Cited By ~ 1

Author(s):

Arjun Gupta ◽

Avash Das ◽

Nivedita Arora ◽

Kaustav Majumder ◽

Preet Paul Singh ◽

...

Keyword(s):

Systematic Review ◽

Morbid Obesity ◽

Body Mass ◽

Meta Analysis ◽

Hepatocellular Cancer ◽

Dependent Manner ◽

Increased Risk ◽

Reported Data ◽

Dose Dependent ◽

Related Mortality

477 Background: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid body mass index (BMI) and HCC mortality. Methods: Through a systematic search of major databases and conference proceedings, up to March 2016, we identified observational studies reporting the association between premorbid BMI, and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CI), comparing obese (BMI > 30 kg/m2) and overweight (BMI 25-29.9 kg/m2) categories with reference category using random effects model; heterogeneity was measured using the inconsistency index (I2). Results: 9 studies were included in which 6,052 HCC deaths occurred in 1,599,453 cancer-free individuals at cohort inception. 5 studies reported data as obese vs. overweight vs. normal BMI, and 4 reported data as obese + overweight combined (BMI > 25 kg/m2). On meta-analysis, pre-morbid obesity was associated with higher HCC-related mortality, as compared to individuals with normal BMI (obese: aHR, 1.96; 95% CI, 1.46-2.46, I2= 37%; overweight: aHR, 1.08; 95% CI, 0.97-1.21, I2= 0%), in dose-dependent manner. This effect was stronger in males [3 studies, aHR, 2.50; 95% CI, 2.02-3.09] vs. females [2 studies, aHR, 1.45; 95% CI, 1.08-1.97]. This effect was seen primarily in Western populations [4 studies, aHR, 2.10; 95% CI, 1.77-2.48], but not in Asian population [1 study, aHR, 1.10; 95% CI, 0.63-1.92]. Conclusions: In this meta-analysis, there was a dose-dependent increase in HCC-related mortality with pre-morbid obesity, particularly in men, and in Western populations. Strategies targeting obesity-induced metabolic abnormalities may provide novel pathways for HCC therapy.

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The Association between Low Muscle Mass and Hepatic Steatosis in Asymptomatic Population in Korea

Life ◽

10.3390/life11080848 ◽

2021 ◽

Vol 11 (8) ◽

pp. 848

Author(s):

Goh-Eun Chung ◽

Hyo-Eun Park ◽

Min-Joo Kim ◽

Min-Sun Kwak ◽

Jong-In Yang ◽

...

Keyword(s):

Hepatic Steatosis ◽

Muscle Mass ◽

Liver Stiffness ◽

Bioelectrical Impedance ◽

Class Ii ◽

Class I ◽

Dependent Manner ◽

Nonalcoholic Fatty Liver ◽

Increased Risk ◽

Dose Dependent

Background: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). Methods: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. Results: Among 960 subjects (58.1 years; 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38–2.78; class II, OR: 3.33, 95% CI: 1.77–6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, <302; OR: 2.19, in CAP ≥ 302; class II, OR: 2.33, for CAP ≥ 248, <302; OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31–2.95; class II, OR: 2.96, 95% CI: 1.51–5.78). Conclusion: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.

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Association of Maternal Serum 25-Hydroxyvitamin D Concentrations with Risk of Gestational Anemia

Cellular Physiology and Biochemistry ◽

10.1159/000481976 ◽

2017 ◽

Vol 43 (4) ◽

pp. 1526-1532 ◽

Cited By ~ 3

Author(s):

Yingdi Yuan ◽

Zhiyong Cai ◽

YaoYao Dai ◽

Qin Hong ◽

Xingyun Wang ◽

...

Keyword(s):

Logistic Regression ◽

Pregnant Women ◽

Maternal Serum ◽

Dependent Manner ◽

Hydroxyvitamin D ◽

Increased Risk ◽

25 Hydroxyvitamin D ◽

Nested Case Control ◽

Dose Dependent ◽

Prevalence Of Anemia

Background/Aims: Vitamin D deficiency has been shown to be associated with a greater prevalence of anemia in various healthy and diseased populations by a great deal of observational studies. However, less work has been done to explore this association in pregnant women. The aim of this study was to evaluate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of gestational anemia in a large, nested case-control study. Methods: The serum 25(OH)D concentrations was measured by enzyme immunoassay in 775 pregnant women affected with anemia and 1550 controls. Logistic regression analysis was conducted to assess the association of 25(OH)D concentrations with risk of gestational anemia. Results: We found the 25(OH)D concentrations was significantly lower in women affected with anemia than in controls. Logistic regression analyses showed that women with 25(OH)D concentrations < 25.0 nmol/L, from 25.0 to 37.4 nmol/L and from 37.5 to 49.9 nmol/L all had increased risk of anemia when compared with women with concentrations from 50.0 to 74.9 nmol/L. And the risk of anemia was significantly increased with the decreasing concentrations of the serum 25(OH)D in a dose-dependent manner (P for trend = 0.012). For women with concentrations < 50.0 nmol/L, they had an 80% increase in anemia risk (95% CI = 1.45-2.25) after adjustment for confounders. We also observed a nonlinear relationship between the serum 25(OH)D and anemia, with a threshold for 25(OH)D of 50.0 nmol/L existed for anemia. Conclusion: Maternal serum 25(OH)D < 50.0 nmol/L may be a risk factor for gestational anemia, and it should be monitored for the high-risk pregnant women.

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73Hemoglobin a1c levels and the risk of ischemic stroke and mortality in individuals with diabetes mellitus and atrial fibrillation

EP Europace ◽

10.1093/europace/euaa162.301 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

L Kezerle ◽

M A Tsadok ◽

A Akriv ◽

B Feldman ◽

M Leventer-Roberts ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Dependent Manner ◽

Historical Cohort ◽

Increased Risk ◽

Dose Dependent ◽

Hba1c Levels

Abstract Funding Acknowledgements Pfizer Israel Background Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Whether the risk of stroke in AF patients remains the same among the wide spectrum of disease is yet to be determined. Aim Among individuals with AF and DM, to assess the incidence rates and risk of ischemic stroke and mortality by baseline HbA1C levels. Methods We conducted a prospective, historical cohort study using the Clalit Health Services (CHS) electronic medical records database. The study population included all CHS members ≥ 21 years old, with a first diagnosis of NVAF between January 1, 2010 to December 31, 2016 and a minimal follow-up period of 1 year. Among those patients identified as diabetics, we compared three groups of patients according to HBA1C levels at the time of AF diagnosis: <7.0%, between 7-9% and ≥ 9%. Results A total of 44,451 cases were identified. The median age was 75 years (IQR 65-83) and 52.5% were women. During a mean follow up of 38 months, the incidence of stroke per 100 person-years in the three study groups was: 1.9 in patients with HBA1C <7%, 2.37 in the intermediary group and 2.72 in those with HBA1C >9%. In both univariate and multivariate analyses, higher levels of HBA1C were associated with an increased risk of stroke compared with a dose-dependent response when compared to individuals with HBA1C <7% (Adjusted Hazard Ratio (AHR) = 1.32 {95% CI 1.12-1.55}for levels between 7-9% and AHR 1.64 {95% CI 1.28-2.09}) even after adjusting for CHA2DS2-VASC individual risk factors and use of oral anti-coagulants. The risk for overall mortality did not differ significantly between groups, with a slight elevation in the HBA1C >9% group after adjusted analysis {aHR = 1.17 (1.07- 1.28)} Conclusion: In this observational cohort of patients with incident newly diagnosed nonvalvular atrial fibrillation, HBA1C levels were associated with an increased risk of stroke in a dose-dependent manner even after accounting for other recognized risk factors for stroke in this population. Abstract Figure. Kaplan-Meier for stroke-free survival

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Dose-Dependent Effect of Platinum-Based Chemotherapy on the Risk of Metachronous Contralateral Testicular Cancer

Journal of Clinical Oncology ◽

10.1200/jco.20.02352 ◽

2020 ◽

pp. JCO.20.02352

Author(s):

Joost M. Blok ◽

Harmke J. Groot ◽

Eline H. Huele ◽

Ronald de Wit ◽

Simon Horenblas ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Cumulative Incidence ◽

Cox Proportional Hazards ◽

Cell Tumor ◽

Inverse Association ◽

Testicular Germ Cell ◽

Platinum Based Chemotherapy ◽

Increased Risk ◽

Dose Dependent

PURPOSE Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk. PATIENTS AND METHODS The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models. RESULTS CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HRper cycle, 0.74; 95% CI, 0.64 to 0.85). CONCLUSION Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk.

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O2D.3 Protective effects of PPE use and good workplace hygiene practices against symptoms of neurotoxicity in collision repair workers

Occupational and Environmental Medicine ◽

10.1136/oem-2019-epi.49 ◽

2019 ◽

Vol 76 (Suppl 1) ◽

pp. A18.3-A19

Author(s):

Samuel Keer ◽

Dave McLean ◽

Bill Glass ◽

Phoebe Taptiklis ◽

James McGlothlin ◽

...

Keyword(s):

Dose Response ◽

Protective Equipment ◽

Dependent Manner ◽

Protective Effects ◽

Body Parts ◽

Solvent Exposure ◽

Hygiene Practices ◽

Increased Risk ◽

Dose Dependent ◽

Reduced Risk

ObjectivesWe have recently shown that solvent-exposed collision repair workers (spray painters and panel beaters) in New Zealand are at an increased risk of both self-reported and objectively assessed neurobehavioural effects, indicating a need for more effective exposure controls. This study assessed the association between personal protective equipment (PPE) use and workplace hygiene and symptoms of neurotoxicity in vehicle spray painters.MethodsExposure controls including PPE-use and workplace hygiene practices and symptoms of neurotoxicity were assessed in 267 vehicle repair spray painters. Symptoms were assessed using the EUROQUEST questionnaire.ResultsFrequent respirator and glove use was inversely associated with symptoms of neurotoxicity in a dose-dependent manner (p<0.05 for trend). The strongest protective effect was found for consistent glove use (OR 0.1and 0.2, p<0.01, for reporting ≥10 and≥5 symptoms, respectively). A dose-response trend (p<0.05) was also observed when combining frequency of respirator and glove use, with an overall reduction in risk of 90% (OR 0.1 for reporting ≥10 and≥5 symptoms, p<0.01) for those who consistently used both. Protective effects were most pronounced for psychosomatic (p<0.05 for trend, for combined PPE use), mood (p<0.05) and memory and concentration symptoms combined (p<0.05), with reductions in risk of >80%. Poor hygiene workplace practices, e.g. solvent exposure to multiple body parts were associated with an increased risk of symptoms, but this was not statistically significant. When using a general workplace hygiene score derived from a combination of PPE-use and (good) workplace hygiene an inverse dose-response trend was observed for reporting ≥5 (p<0.01) and ≥10 symptoms (p<0.01).ConclusionsThis study has shown that PPE-use and good workplace hygiene are associated with a strongly reduced risk of symptoms of neurotoxicity in solvent-exposed vehicle spray painters. Glove use was most protective, suggesting dermal exposures may be of particular importance in the development of symptoms.

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QT prolongation: Which psychotropics?

European Psychiatry ◽

10.1016/s0924-9338(11)72937-6 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1232-1232

Author(s):

J. Campos Mendes ◽

J. Prata

Keyword(s):

Psychiatric Patients ◽

Torsades De Pointes ◽

Experimental Models ◽

Delayed Rectifier ◽

Dependent Manner ◽

Drug Induced ◽

Increased Risk ◽

Surface Ecg ◽

Common Causes ◽

Dose Dependent

Prolongation of the ventricular repolarisation manifests itself as a prolongation of the QT intervall on the surface ECG and represents a major risk for a special form of ventricular tachycardia called “torsades de pointes”, that are often self limited and are associated with palpitations, dizziness or syncope, but degeneration into ventricular fibrillation and sudden cardiac death can occur. Psychotropics are among the most common causes of drug induced acquired long QT syndrome. Blockage of Human ether-a-go-go-related gene (HERG) potassium channel by psychoactive drugs appears to be related to this adverse effect. Antipsychotics such as haloperidol, thioridazine, sertindole, pimozide, risperidone, ziprasidone, quetiapine, olanzapine and antidepressants such as amitriptyline, imipramine, doxepin, trazadone, fluoxetine depress the delayed rectifier potassium current (IKr) in a dose dependent manner in experimental models. The frequency of QTc prolongation (more than 456ms) in psychiatric patients is estimated to be 8%. In large epidemiological controlled studies a dose dependent increased risk of sudden death has been identified in current users of antipsychotics (conventional and atypical) and of TCA. The authors propose to further explore this theme, in a review of existing literature.

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Paternal age, size at birth, and size in young adulthood – risk factors for schizophrenia

Acta Endocrinologica ◽

10.1530/eje.1.02264 ◽

2006 ◽

Vol 155 (suppl_1) ◽

pp. S65-S69 ◽

Cited By ~ 10

Author(s):

Finn Rasmussen

Keyword(s):

Young Adulthood ◽

Record Linkage ◽

Military Service ◽

De Novo ◽

Neurodevelopmental Disorder ◽

Paternal Age ◽

Fetal Life ◽

Medical Birth Register ◽

Causal Pathways ◽

Increased Risk

It is appropriate to consider schizophrenia a neurodevelopmental disorder with its pathogenesis going back to gestation and early childhood. Schizophrenia is a rare disease and large cohorts are needed to study its etiology. The aim of this paper is to review the results of recent Swedish record-linkage studies with a focus on: (i) measures of fetal and childhood growth in relation to schizophrenia in adulthood and (ii) paternal age in relation to schizophrenia. A record-linkage was created between national registers, including the Medical Birth Register, the Military Service Conscription Register, and the Inpatient Hospital Discharge Register. More than 700 000 subjects born between 1973 and 1980 were followed in these registers from birth to 31 December 2001/2002. The results showed no evidence of an association between birth weight and schizophrenia. An association of birth length with schizophrenia was observed, with short babies showing the highest risk. Short stature and low BMI in young adulthood were associated with increased risk. Short babies who became tall, or developed high BMI as adults, were not at increased risk. In fully adjusted analyses, the risk of schizophrenia was 4.62 (95% confidence interval : 2.28; 9.36) times higher in subjects whose fathers were ≥50 years old and at time of conception than in subjects whose fathers were 21–24 years old. Growth and development in fetal life and childhood are influencing the risk of schizophrenia in adulthood, but the underlying causal pathways are still unknown. De novo mutations in the germ cells of older fathers may play a causal role in the etiology of some cases of schizophrenia.

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