scholarly journals A Novel Model of Schizophrenia Age-of-Onset Data Challenges the Conventional Interpretations of the Discordance in Monozygote Twin Studies

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ivan Kramer ◽  
L. Elliot Hong
Keyword(s):  
Age Of Onset ◽  
Disease Onset ◽  
Twin Studies ◽  
Concordance Rate ◽  
Early Environment ◽  
Mutation Model ◽  
Environmental Contribution ◽  
Novel Model ◽  
Susceptible Gene ◽  
Genetic Hypothesis

The relative importance of genetics and the environment in causing schizophrenia is still being debated. Although the high proportion of monozygote cotwins of schizophrenia patients who are discordant suggests that there may be a significant environmental contribution to the development of schizophrenia, this discordance is predicted by an accumulative multimutation model of schizophrenia onset constructed here implying a genetic origin of schizophrenia. In this model, schizophrenics are viewed as having been born with the genetic susceptibility to develop schizophrenia. As susceptible gene carriers age, they randomly accumulate the necessary mutations to cause schizophrenia, the last needed mutation coinciding with disease onset. The mutation model predicts that the concordance rate in monozygote twin studies will monotonically increase with age, theoretically approaching 100% given sufficient longevity. In dizygote cotwins of schizophrenia patients, the model predicts that at least 71% of cotwins are incapable of developing schizophrenia even though every cotwin and their schizophrenic twin shared a similar early environment. The multimutation model is shown to fit all of the monozygote and dizygote concordance rate data of the principle classical twin studies completed before 1970 considered in this paper. Thus, the genetic hypothesis of schizophrenia can be tested by bringing these studies up to date.

scholarly journals A Genetic Multimutation Model of Autism Spectrum Disorder Fits Disparate Twin Concordance Data from the USA and Canada

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Ivan Kramer ◽  
Paul H. Lipkin ◽  
Alison R. Marvin ◽  
Paul A. Law
Keyword(s):  
Autism Spectrum Disorder ◽  
Age Of Onset ◽  
Autism Spectrum ◽  
Concordance Rate ◽  
Spectrum Disorder ◽  
Critical Test ◽  
The Usa ◽  
Males And Females ◽  
Kennedy Krieger Institute ◽  
Genetic Hypothesis

Whether autism spectrum disorder (ASD) is caused by genetics, environmental factors, or a combination of both is still being debated today. To help resolve this issue, a genetic multimutation model of ASD development was applied to a wide variety of age-of-onset data from the USA and Canada, and the model is shown to fit all the data. Included in this analysis is new, updated data from the Interactive Autism Network (IAN) of the Kennedy Krieger Institute in Baltimore, Maryland. We find that the age-of-onset distribution for males and females is identical, suggesting that ASD may be an autosomal disorder. The ASD monozygote concordance rate in twin data predicted by the genetic multimutation model is shown to be compatible with the observed rates. If ASD is caused entirely by genetics, then the ASD concordance rate of a cohort of monozygote twins should approach 100% as the youngest pair of twins in the cohort passes 10 years of age, a prediction that constitutes a critical test of the genetic hypothesis. Thus, by measuring the ASD concordance rate as a cohort of monozygote twins age, the hypothesis that this disorder is caused entirely by genetic mutations can be tested.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

scholarly journals Family burden in schizophrenia: the influence of age of onset and negative symptoms

2016 ◽  
Vol 38 (2) ◽  
pp. 96-99 ◽  
Author(s):  
Lucas M. Mantovani ◽  
Rodrigo Ferretjans ◽  
Iara M. Marçal ◽  
Amanda M. Oliveira ◽  
Fernanda C. Guimarães ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Age Of Onset ◽  
Linear Regression Analysis ◽  
Disease Onset ◽  
Family Burden ◽  
Positive Symptoms ◽  
Subjective Burden ◽  
Sociodemographic Variables ◽  
Objective Burden ◽  
Positive And Negative Symptoms

Abstract Objectives: To investigate the determinants of family burden in a sample of patients with schizophrenia and their caregivers. Methods: Thirty-one stable patients with schizophrenia and their main caregivers were recruited. Sociodemographic variables were assessed in a semi-structured interview, and positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed with the Schizophrenia Cognition Rating Scale (SCoRS). Levels of burden on caregivers were assessed with the Family Burden Interview Schedule (FBIS). Interactions among variables were analyzed using Pearson correlations and linear regression analysis. Results: Objective and subjective FBIS scores were 1.9 (standard deviation [SD] = 0.5) and 2.4 (SD = 0.6) respectively. Objective burden correlated positively with positive and negative symptoms, and cognitive impairment. Subjective burden correlated positively with positive symptoms and negatively with mean age of disease onset. Positive, negative and cognitive symptoms accounted for 47.6% of the variance of objective burden, with negative symptoms accounting independently for 30.3%. Age of onset, parents as caregivers and positive symptoms accounted for 28% of the variance of subjective burden, with age of onset independently explaining 20.3%. Conclusion: Patients' clinical and sociodemographic variables are important determinants of family burden in schizophrenia. Objective burden is predicted by symptoms, particularly negative ones. Subjective burden is predicted by symptoms and sociodemographic variables, particularly age of disease onset.

scholarly journals Familial Aggregation in Idiopathic Subglottic Stenosis

2020 ◽  
Vol 163 (5) ◽  
pp. 1011-1017
Author(s):  
Virginia E. Drake ◽  
Alexander Gelbard ◽  
Nara Sobriera ◽  
Elizabeth Wohler ◽  
Lynne L. Berry ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Familial Aggregation ◽  
Tertiary Care ◽  
Positive Family History ◽  
Disease Onset ◽  
Subglottic Stenosis ◽  
Patient Demographics ◽  
The North ◽  
Familial Clustering ◽  
Tertiary Care Centers

Objective To evaluate inheritance patterns and define the familial clustering rate of idiopathic subglottic stenosis (iSGS). Study Design Retrospective observational study. Setting International multicenter collaborative of >30 tertiary care centers. Methods Patients with a clinically confirmed iSGS diagnosis within the North American Airway Collaborative’s iSGS1000 cohort consented between 2014 and 2018 were eligible for enrollment. Patient demographics and disease severity were abstracted from the collaborative’s iSGS longitudinal registry. Pedigrees of affected families were created. Results A total of 810 patients with iSGS were identified. Positive family history for iSGS was reported in 44 patients in 20 families. The rate of familial clustering in iSGS is 2.5%. Mean age of disease onset is 42.6 years. Of the 44 patients with familial aggregation of iSGS, 42 were female and 2 were male; 13 were mother-daughter pairs and 2 were father-daughter pairs. There were 3 sister-sister pairs. There was 1 niece-aunt pair and 2 groups of 3 family members. One pedigree demonstrated 2 affected mother-daughter pairs, with the mothers being first-degree paternal cousins. Inheritance is non-Mendelian, and anticipation is present in 11 of 13 (84%) parent-offspring pairs. The mean age of onset between parents (48.4 years) and offspring (36.1 years) was significantly different ( P = .016). Conclusion This study quantifies the rate of familial clustering of iSGS at 2.5%. Inheritance is non-Mendelian, and disease demonstrates anticipation. These data suggest that there may be a genetic contribution in iSGS.

scholarly journals Progressive supranuclear palsy in a sample of brazilian population: clinical features of 16 patients

2002 ◽  
Vol 60 (4) ◽  
pp. 917-922 ◽  
Author(s):  
Paulo Eduardo Mestrinelli Carrilho ◽  
Egberto Reis Barbosa
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Clinical Features ◽  
Age Of Onset ◽  
Disease Onset ◽  
Final Diagnosis ◽  
Postural Instability ◽  
Chronic Dacryocystitis ◽  
Neurologic Disorders ◽  
The Mean ◽  
Vertical Gaze

Progressive supranuclear palsy (PSP) is an uncommon disorder characterized by marked postural instability, vertical gaze abnormalities and axial rigidity. The purpose of this study is to report the clinical features of 16 consecutive subjects seen over a 10-year period at a Movement Disorders Clinic. These subjects fulfilled criteria for probable PSP namely those of the National Institute of Neurologic Disorders and Stroke (NINDS) and the Society for PSP (SPSP). This patient-group represented 2.1% of all degenerative parkinsonians observed and the mean age of onset of the disease was 64.7 years (sd = ± 7.2). Postural instability with falls was the most frequent initial feature presented in PSP patients (62.5%). The hallmark of the disease, the supranuclear vertical gaze palsy, appeared after 2.3 years of disease onset, and only 12.5% had such manifestation at the first evaluation. Transient tremor was observed with a relatively high frequency in this group (44%), but only 19% had rest tremor. Chronic dacryocystitis, probably related to a paucity of blinking, was observed in two patients as an inaugural manifestation. In the first evaluation, only 19% of the 16 patients were diagnosed as probable PSP. The mean interval prior to the final diagnosis was 2.4 years.

Superior survival of breast cancer BRCA1 /2 mutation carriers harboringG/G at the -309 position at the MDM2 promoter compared to those harboring T/T or G/T at this SNP

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10600-10600
Author(s):  
H. Nechushtan ◽  
T. Hamburger ◽  
S. Mendelson ◽  
L. Kadouri ◽  
N. Sharon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Germ Line ◽  
Age Of Onset ◽  
Disease Onset ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Mdm2 Snp309 ◽  
Li Fraumeni Syndrome ◽  
Mutation Carriers

10600 Background: A germ line single polymorphism in the promoter of the gene encoding the important modulator of P53, MDM2 has been described. The findings of G/G nucleotides at this position in contrast to G/Tor T/T were demonstrated to increase MDM2 transcriptional levels and were correlated with younger onset of cancers in patients with the Li-Fraumeni syndrome. Furhtermore gastric cancer patients harboring T/T at this position and treated with chemotherapy were found to have decresed survival compared to the other SNP carriers. P53 mutations appear in high frequency in tumors associated with BRCA1/2 mutations. Indeed it has been suggested that mutations in the p53 gene are a necessary step in tumorigenesis in BRCA tumors. Methods: Here we investigate the effect of the MDM2 SNP309 on overall survival and age of onset in breast cancer patients. MDM2 SNP309 was evaluated in Breast cancer Ashkenazy patients analyzed for the three common mutations in BRCA1/2- 180 patients who are positive for either of these mutation and 272 negative ones. 194 negative, Disease onset age and survival were analyzed for the different subgroups Results: Around a quarter of the whole population analyzed were identified as carriers of G/G at the -309 MDM2. There was no correlation between age of disease onset in either BRCA1/2mutation carriers and the specific genotype. In the BRCA1/2 mutation carriers we found a survival advantage in patients harboring the SNP309 G/G genotype(p-0.001 log rank test). Such an effect was not demonstrated in patients tested negative for the known Ashkenazy mutations Conclusions: In specific subgroups of breast cancer patients SNP309 G/G is associated with improved patient survival. A possible explanation for this finding could be the presence of a P53 which can be reactivated in the MDM2 SNP309 G/G carriers. No significant financial relationships to disclose.

scholarly journals Locomotor activity and gait in aged mice deficient for type IX collagen

2010 ◽  
Vol 109 (1) ◽  
pp. 211-218 ◽  
Author(s):  
Kerry E. Costello ◽  
Farshid Guilak ◽  
Lori A. Setton ◽  
Timothy M. Griffin
Keyword(s):  
Locomotor Activity ◽  
Wheel Running ◽  
Age Of Onset ◽  
Disease Onset ◽  
Stride Frequency ◽  
Dark Phase ◽  
Running Wheel ◽  
Voluntary Activity ◽  
Knee Oa ◽  
Locomotor Behaviors

Osteoarthritis (OA) is a risk factor for physical inactivity and impaired mobility, but it is not well understood how these locomotor behaviors are affected by the age of onset of OA and disease severity. Male mice homozygous for a Col9a1 gene inactivation ( Col9a1−/−) develop early onset knee OA, increased tactile pain sensitivity, and gait alterations by 9 mo of age. We hypothesized that aged Col9a1−/− mice would reduce joint pain by adopting locomotor behaviors that reduce both the magnitude and daily frequency of joint loading. We tested this hypothesis by evaluating gait and spontaneous locomotor activity in 15- to 17-mo-old male Col9a1−/− ( n = 5) and Col9a1+/+(WT) ( n = 5) mice using well-controlled measures of voluntary activity in overground and running wheel conditions, as well as studies of gait in a velocity-controlled treadmill. We found no difference due to genotype in freely chosen locomotor velocity, stride frequency, hindfoot duty factor, dark phase activity time, or dark-phase travel distance during overground, running wheel, or speed-matched treadmill locomotion. Interpretation of these findings is potentially confounded by the observation that WT mice have greater knee OA than Col9a1−/− mice in the lateral tibial plateau by 17 mo of age. When accounting for individual differences in knee OA, functional locomotor impairments in aged Col9a1−/− and WT mice are manifested as reductions in total locomotor activity levels (e.g., both distance traveled and time active), particularly for wheel running. These results support the concept that current disease status, rather than age of disease onset, is the primary determinant of impaired locomotor activity with aging.

Defining discordance in twin studies of risk and protective factors for late life disorders

Twin Research ◽  
2000 ◽  
Vol 3 (3) ◽  
pp. 159-164 ◽  
Author(s):  
Margaret Gatz ◽  
Nancy L Pedersen ◽  
Michael Crowe ◽  
Amy Fiske
Keyword(s):  
Protective Factors ◽  
Age Of Onset ◽  
Twin Studies ◽  
Matched Pair ◽  
Considerable Influence ◽  
Matched Pair Analysis ◽  
Causes Of Mortality ◽  
Competing Causes ◽  
Definition Of ◽  
Pair Analysis

AbstractIn studies that employ matched pair analysis to identify environmental exposures important for a disorder, criteria for discordant pairs are seldom discussed. Yet several assumptions concerning the definition of discordancy may have considerable influence over what results are found. Problems are exacerbated when age of onset for a disorder is late in life. We propose a new set of criteria for defining discordant pairs in studies of dementia, taking into account duration of discordance and competing causes of mortality, and evaluate the consequences of choosing alternative definitions of discordancy. Twin Research (2000) 3, 159–164.

scholarly journals Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome

2021 ◽  
Vol 11 (9) ◽  
pp. 1223
Author(s):  
Florence Lai ◽  
Nathaniel D. Mercaldo ◽  
Cassandra M. Wang ◽  
Micaela S. Hersch ◽  
Giovi G. Hersch ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Alzheimer Disease ◽  
Age Of Onset ◽  
Disease Onset ◽  
Age Groups ◽  
Positive Association ◽  
Early Age ◽  
Thyroid Function Tests ◽  
Logistic Regression Models ◽  
Chi Squared

Adults with Down syndrome (DS) have an exceptionally high frequency of Alzheimer disease (AD) with a wide variability in onset, from 40 to 70 years of age. Equally prevalent in DS is hypothyroidism. In this study, we sought to quantify the relationship between the two. A total of 232 adults with DS and AD were stratified into three AD onset age groups: early (<47 years), typical (48–59), and late (>59). Among patients with available data, differences in the distributions of demographics, hypothyroidism variables (presence, age of onset), thyroid function tests, thyroid autoantibodies, and APOE genotypes were assessed (e.g., chi-squared, Mann–Whitney tests). Spearman and partial Spearman correlations and ordinal logistic regression models were constructed to quantify the association between ages of AD and hypothyroidism onset with and without covariate adjustments. We observed a positive association between the ages of AD and hypothyroidism onset after accounting for APOE-Ɛ4 (correlation: 0.44, 0.24, 0.60; odds ratio: 1.09, 1.05–1.14). However, an early age of hypothyroidism onset and the presence of the APOE-Ɛ4 allele were independently associated with the early age of AD onset. Similar findings were observed when accounting for other factors. Our study provides evidence for the importance of hypothyroidism and associated pathological mechanisms for risk of AD in DS.

scholarly journals MIND diet associated with later onset of Parkinson's disease

2020 ◽  
Author(s):  
Avril Metcalfe-Roach ◽  
Adam Yu ◽  
Ella Golz ◽  
Kristen Sundvick ◽  
Mihai Cirstea ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mediterranean Diet ◽  
Dietary Habits ◽  
Age Of Onset ◽  
Disease Onset ◽  
Cross Sectional ◽  
Diet Adherence ◽  
The Mind ◽  
Mind Diet

Background: The MIND diet has been linked with prevention of Alzheimer's disease and cognitive decline but has not been fully assessed in the context of Parkinson's disease (PD). Objective: To determine whether MIND diet adherence is associated with the age of Parkinson's disease onset in a manner superior to that of the Mediterranean diet. Methods: Food Frequency Questionnaires from 167 participants with PD and 119 controls were scored for MIND and two versions of Mediterranean diet adherence. Scores were compared between sex and disease subgroups, and PD diet adherence was correlated with age of onset using univariate and multivariate linear models. Results: The female subgroup adhered more closely to the MIND diet than the males, and diet scores were not modified by disease status. Later age of onset correlated most strongly with MIND diet adherence in the female subgroup, corresponding to differences of up to 17.4 years (p<0.001) between low and high dietary tertiles. Greek Mediterranean adherence was also significantly associated with later PD onset across all models (p=0.05-0.03). Conversely, only Greek Mediterranean adherence remained correlated with later onset across all models in men, with differences of up to 8.4 years (p=0.002). Conclusions: This cross-sectional study finds a strong correlation of age of onset of PD with dietary habits, suggesting that nutritional strategies may be an effective tool to delay PD onset. Further studies may help to elucidate potential nutrition-related sex-specific pathophysiological mechanisms and differential prevalence rates in PD.

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