Abstract P650: Increased Genetic Risk for Venous Thromboembolism is Associated With Early Onset Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Thomas J Jaworek ◽  
Brady Gaynor ◽  
Huichun Xu ◽  
John W Cole ◽  
O. C Stine ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Venous Thromboembolism ◽  
Genetic Risk ◽  
Early Onset ◽  
Fixed Effects ◽  
Age Of Onset ◽  
Late Onset ◽  
Risk Scores ◽  
P Value ◽  
Polygenic Risk Score

Intro: In the Early Onset Stroke Consortium (EOSC) trans-ancestry analysis we found the ABO locus to be strongly associated with early onset stroke (rs529565, OR=1.10, p-value= 2.01 x 10-12). The lead SNP at this locus has a significantly larger effect size in early onset cases compared to stroke cases after age sixty and is independently associated with venous thromboembolism. This finding, in addition with previously reported candidate gene studies ( F5 , F11 , PROCR ), suggests that coagulation and hemostasis related pathways may be a major driver of early onset stroke. Motivation: To examine the genetic relationship between VTE risk burden and early onset stroke, we performed a polygenic risk score analysis to determine whether increased genetic risk for VTE was also more strongly associated with early compared to late age of onset stroke. Methods: Weighted VTE polygenetic risk scores based on recent GWAS of VTE were calculated for each individual in 7K early onset, under age 60, stroke cases from the EOSC and in 9K late onset, ages 60 and older, stroke cases from SiGN. Logistic regression was performed to test the association between the VTE-PRS score and ischemic stroke outcome controlling for sex and the first ten principal components to account for ancestry. Analyses were stratified by age of onset. Fixed effects meta-analysis was performed to combined results across the analysis strata. Results: PRS of VTE was associated with early ischemic stroke (OR=1.11, p-value=0.02) and we saw no association between VTE-PRS and late onset stroke (OR=1.04, p-value=0.5). Early cases had a greater PRS of VTE than late cases (p-value=0.01). Conclusion: While VTE has been shown to associate with stroke risk, we observed a greater genetic risk for VTE in early onset ischemic stroke compared to older onset stroke. This complements existing evidence implicating coagulation-related mechanisms as an important genetic mechanism in early onset strokes.

scholarly journals Genetic Contributions to Early and Late Onset Ischemic Stroke

2021 ◽  
Author(s):  
Thomas Jaworek ◽  
Huichun Xu ◽  
Brady Gaynor ◽  
John Cole ◽  
Kristiina Rannikmae ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Venous Thromboembolism ◽  
Blood Group ◽  
Early Onset ◽  
Late Onset ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Blood Group A ◽  
Genome Wide ◽  
Group A

Abstract Objective: To determine the contribution of common genetic variants to risk of early onset ischemic stroke (IS). Methods: We performed a meta-analysis of genome-wide association studies of early onset IS, ages 18-59, using individual level data or summary statistics in 16,927 cases and 576,353 non-stroke controls from 48 different studies across North America, Europe, and Asia. We further compared effect sizes at our most genome-wide significant loci between early and late onset IS and compared polygenic risk scores for venous thromboembolism between early versus later onset IS. Results: We observed an association between early onset IS and ABO, a known stroke locus. The effect size of the peak ABO SNP, rs8176685, was significantly larger in early compared to late onset IS (OR 1.17 (95% C.I.: 1.11-1.22) vs 1.05 (0.99-1.12); p for interaction = 0.008). Analysis of genetically determined ABO blood groups revealed that early onset IS cases were more likely to have blood group A and less likely to have blood group O compared to both non-stroke controls and to late onset IS cases. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with early, compared to late, onset IS (p=0.008). Conclusion: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with early onset IS, compared with late onset IS, supporting a stronger role of prothrombotic factors in early onset IS.

Abstract P663: Polygenic Risk Scores for Plasma Levels of Fibrin D-Dimer and Tissue Plasminogen Activator Are Associated With Non-Lacunar Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Yonit A Addissie ◽  
Brady Gaynor ◽  
Thomas Jaworek ◽  
Huichun Xu ◽  
Colin O Stine ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Plasma Levels ◽  
Early Onset ◽  
Late Onset ◽  
Plasma Concentrations ◽  
Risk Scores ◽  
Lacunar Stroke ◽  
Related Factors ◽  
Pai 1 ◽  
D Dimer

Introduction: Plasma concentrations of prothrombotic factors such as fibrinogen have previously been associated with ischemic stroke risk. To extend this observation, we examined the association of polygenic risk scores (PRS) for increased plasma levels of thrombosis-related factors with ischemic stroke. Our hypotheses were that these PRS would be more associated with early than late onset stroke and with non-lacunar than lacunar stroke. Methods: We identified 9053 late onset (≥ 60 years) stroke cases from the NINDS International Stroke Genetics Consortium (SiGN) with 24804 controls and 6594 early onset (< 60 years) stroke cases from the Genetics of Early Onset Ischemic Stroke Consortium with 30561 controls. We identified previously known loci associated with plasma levels of four thrombosis-related factors: fibrinogen, fibrin D-dimer, tPA and PAI-1 from prior GWAS studies and developed genome-wide PRS for plasma concentrations of these factors. We then used logistic regression to test the association of these scores with risk of stroke and stroke subtype. Results: PRS for fibrin D dimer levels were associated with increased risk for all stroke and specifically for older (p = 0.019), but not younger (p = 0.22) onset stroke. PRS for tPA levels were also marginally associated with older (p = 0.06), but not younger (p = 0.24) onset stroke. Genetic risk scores for both D dimer and tPA were associated with non-lacunar stroke (Table 1). Further analyses stratified by age revealed PRS for D dimer to be significantly associated with non-lacunar stroke (but not lacunar stroke) in both late and early onset cohorts. PRS for fibrinogen and PAI-1 were not associated with stroke. Conclusion: Genomic risk scores for thrombosis-related factors including D dimer and tPA levels were associated with risk for ischemic stroke, and specifically, non-lacunar stroke.

scholarly journals Association of Admission Temperature and Outcome among Neonates with Sepsis in a Tertiary Care Hospital

2020 ◽  
Vol 35 (2) ◽  
pp. 150-155
Author(s):  
Mahfuza Shirin ◽  
M Monir Hossain ◽  
Manifa Afrin
Keyword(s):  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Mild Hypothermia ◽  
Tertiary Care ◽  
P Value ◽  
Moderate Hypothermia ◽  
Care Hospital ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis

Background: Neonatal sepsis is one of the major causes of mortality in neonates. Hypothermia is also an important contributing factor of neonatal mortality. Neonates with sepsis can present with normal temperature, hypo or hyperthermia. Objectives: This study was design to find out the pattern of temperature on admission and its association with mortality among neonates admitted with sepsis. Methods: This cross-sectional study was conducted from September 2017 to April 2018 in the Department of Neonatal Medicine and NICU, Dhaka Shishu (Children) Hospital. Neonates up to thirty days of age, diagnosed as probable sepsis were enrolled. On admission, axillary temperature was recorded for 3 minutes and neonates were categorized according to the recorded temperature. Neonates were classified as early onset sepsis (EOS) and late onset sepsis (LOS) according to the age of onset of the sepsis. Outcome was also recorded. Statistical analysis was done by SPSS program version 25. Chi-square (X2) test was done to determine the association and p value, <0.05 was taken as significant. Results: Among 493 enrolled neonates, 41.2% neonates were with early onset sepsis (EOS) and 58.8% were with late onset sepsis (LOS). Out of 493 neonates, 89(18.1%) died. Among the enrolled neonates, 54.4% had normal temperature, 16.6% had mild hypothermia, 14.6% had moderate hypothermia and 14.4% had hyperthermia. It was found that mild and moderate hypothermia were significantly more in EOS(p<0.05). Mortality was significantly high in neonates with mild and moderate hypothermia (p<0.05). Conclusion: This study found that mortality was associated with mild and moderate hypothermia in neonates admitted with sepsis. DS (Child) H J 2019; 35(2) : 150-155

scholarly journals Polygenic Risk Score of Sporadic late Onset Alzheimer Disease Reveals a Shared Architecture with the Familial and Early Onset Forms

2017 ◽  
Author(s):  
Jorge L Del-Aguila ◽  
Benjamin Saef ◽  
Kathleen Black ◽  
Maria Victoria Fernandez ◽  
John Budde ◽  
...  
Keyword(s):  
Early Onset ◽  
Genetic Architecture ◽  
Late Onset ◽  
Age At Onset ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Risk Variants ◽  
Genome Wide ◽  
Load Risk

AbstractObjective:To determine whether the genetic architecture of sporadic late-onset Alzheimer’s Disease (sLOAD) has an effect on familial late-onset AD (fLOAD), sporadic early-onset (sEOAD) and autosomal dominant early-onset (eADAD).Methods:Polygenic risk scores (PRS) were constructed using previously identified 21 genome-wide significant loci for LOAD risk.Results:We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. sEOAD showed the highest odds for the PRS (OR=2.27; p=1.29×10-7), followed by fLOAD (OR=1.75; p=1.12×10-7) and sLOAD (OR=1.40; p=1.21×10-3). PRS is associated with cerebrospinal fluid ptau181-Aβ42on eADAD.Conclusion:Our analysis confirms that the genetic factors identified for sLOAD also modulate risk in fLOAD and sEOAD cohorts. Furthermore, our results suggest that the burden of these risk variants is associated with familial clustering and earlier-onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset.

THE RELATIONSHIP BETWEEN THE ONSET OF SEVERE PREECLAMPSIA AND PERINATAL COMPLICATIONS AT RUMKITAL Dr. RAMELAN IN SURABAYA

2021 ◽  
Vol 5 (2) ◽  
pp. 139
Author(s):  
Widya Retno ◽  
Ivon Diah Wittiarika ◽  
Muhammad Aldika Akbar
Keyword(s):  
Preterm Delivery ◽  
Early Onset ◽  
Late Onset ◽  
Previous History ◽  
Severe Preeclampsia ◽  
P Value ◽  
Chronic Hypertension ◽  
Perinatal Complications ◽  
Exact Test ◽  
The Relationship

 Abstract Background: Preeclampsia is one of the biggest causes of maternal-fetal morbidity and mortality. Based on the prognosis, the classification of Preeclampsia is early onset (<34 weeks) and late onset (> 34 weeks). Purpose: to investigate the relationship between the onset of severe Preeclampsia and perinatal complications. Method: This research is a quantitative study with a retrospective observational analytic study type and collected medical record data. The study population was severe Preeclampsia  patients who gave birth at RUMKITAL Dr. Ramelan Surabaya for the period January 2018 - June 2020 and has no previous history of chronic hypertension. The research sample was 79 subjects with 44 subjects early onset, and 35 subjects late onset. Perinatal complications  examined are preterm delivery, asphyxia, LBW, IUGR, stillbirth. The chi-square test or Fisher’s Exact Test was used to analyze relationships. Result: From the results of the study, the comparison of the percentage from early onset and late onset that experienced complications was 93.2% vs 48.6%, p-value = 0.000, OR = 14.5, CI = 3,764–55,635.  At preterm delivery, it was found that 75% vs 28.6%, p-value = 0.000,  OR = 7.5, CI = 2,754-20,422. . In asphyxia, it was found 41.7% vs 31.4%, p-value = 0.46. At LBW, it was found 72.7% vs 17.1%, p-value = 0,000, OR = 12.9, CI = 4,285-38,771. In IUGR, it was found that 15.9% vs 2.9%, p-value = 0.000. In stillbirth, it was found 18.2% vs 0% and p-value = 0.008. Conclusion: the onset of severe Preeclampsia is related with perinatal complications. Complications associated with the onset severe Preeclampsia are preterm, LBW, stillbirth. Meanwhile, complications that are not related with the onset severe Preeclampsia are asphyxia and IUGR  

Age, Age of Onset and Course of Primary Depressive Illness in the Elderly*

1983 ◽  
Vol 28 (2) ◽  
pp. 102-104 ◽  
Author(s):  
Martin G. Cole
Keyword(s):  
Elderly Patients ◽  
Depressive Episode ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
The Elderly ◽  
Depressive Illness ◽  
Physical Illness ◽  
Course Of Illness

Thirty-eight elderly patients with primary depressive illness (Feighner criteria) were followed up for 7–31 months. In the absence of persistent organic signs and severe physical illness, age of onset (first depressive episode after 60) but not age was significantly related to course of illness. Compared to early onset depressives, late onset depressives were more likely to remain completely well during the follow-up period and less likely to have frequent or disabling relapses.

Early and Late Onset Bipolar Disorders in Older Adults

2017 ◽  
Vol 41 (S1) ◽  
pp. S211-S211
Author(s):  
N. Smaoui ◽  
L. Zouari ◽  
N. Charfi ◽  
M. Maâlej-Bouali ◽  
N. Zouari ◽  
...  
Keyword(s):  
Older Adults ◽  
Bipolar Disorder ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Age At Onset ◽  
Bipolar Disorders ◽  
Medical Diagnoses ◽  
The Mean ◽  
Bipolar Patients

IntroductionAge of onset of illness may be useful in explaining the heterogeneity among older bipolar patients.ObjectiveTo examine the relationship of age of onset with clinical, demographic and behavioral variables, in older patients with bipolar disorder.MethodsThis was a cross-sectional, descriptive and analytical study, including 24 patients suffering from bipolar disorders, aged 65 years or more and followed-up in outpatient psychiatry unit at Hedi Chaker university hospital in Sfax in Tunisia. We used a standardized questionnaire including socio-demographic, behavioral and clinical data. Age of onset was split at age 40 years into early-onset (< 40 years; n = 12) and late-onset (≥ 40 years; n = 12) groups.ResultsThe mean age for the entire sample was 68.95 years. The mean age of onset was 39.95 years. The majority (60%) of patients were diagnosed with bipolar I. Few meaningful differences emerged between early-onset and late-onset groups, except that tobacco use was significantly higher in the late-onset group (66.6% vs. 16.6%; P = 0.027). No significant differences between the early-onset and late-onset groups were seen on demographic variables, family history and number of medical diagnoses or presence of psychotic features.ConclusionOur study found few meaningful behavioral differences between early versus late age at onset in older adults with bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Maternofetal outcomes in early versus late onset pre-eclampsia: a comparative study

2019 ◽  
Vol 8 (2) ◽  
pp. 548
Author(s):  
Poornima Shankar ◽  
Kavitha Karthikeyan ◽  
Amrita Priscilla Nalini ◽  
Sindhura M. ◽  
Gowtham Kim
Keyword(s):  
Risk Factors ◽  
Gestational Age ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Fetal Outcomes ◽  
Chi Square ◽  
Onset Type ◽  
Significant Difference ◽  
Early Onset Preeclampsia

Background: Preeclampsia is being increasingly recognized as two different entities: early-onset preeclampsia occurring at less than 34 weeks of gestation, and late-onset disease occurring at 34 or more weeks of gestation. Early-onset and late-onset pre-eclampsia are found to have different implications for the mother and neonate. The aim of this study is to compare the risk factors, maternal and fetal outcomes in early (<34 weeks) versus late (≥34weeks) onset preeclampsia.Methods: 208 patients diagnosed with pre-eclampsia in Chettinad Academy of Research and Education over a period of three years (From January 2014 to December 2016) were retrospectively studied. Patients were classified as early onset and late onset pre-eclampsia based on the gestational age of onset. Data on risk factors, maternal and fetal outcomes were collected and analyzed using Chi Square and Fisher’s test and compared.Results: The overall preeclampsia rate was 6.3%. Early onset and late onset were 34.6% and 65.3% respectively and the rate increased with increasing gestational age.35.3% of patients with late onset preeclampsia and 55.6% patients of early onset type required more than one drug which is a statistically significant difference. Proteinuria more than 3gm/l/day was significantly more in late onset preeclampsia than in early onset preeclampsia. 55.5% of patients with early onset pre-eclampsia required MgSO4 when compared to 17.4%. There was no statistically significant difference in the rate of caesarean section (61.1% vs 73.5%). Altered coagulation profile was significantly more in early onset preeclampsia (11.1%). The incidence of oligohydramnios, SGA and low APGAR at 5 minutes of birth were significantly high in early onset pre-eclampsia when compared to late onset type.Conclusions: Patients with early onset pre-eclampsia are found to have significantly higher rates of specific maternal and fetal morbidity when compared to the late onset type.

scholarly journals Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer

2019 ◽  
Vol 20 (4) ◽  
pp. 968 ◽  
Author(s):  
Edurne Álvaro ◽  
Juana M. Cano ◽  
Juan L. García ◽  
Lorena Brandáriz ◽  
Susana Olmedillas-López ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Cpg Island ◽  
Low Frequency ◽  
Tumor Location ◽  
Molecular Characteristics ◽  
Braf Mutations ◽  
Rectal Cancers

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification.

scholarly journals Altered Proteolysis in Fibroblasts of Alzheimer Patients with Predictive Implications for Subjects at Risk of Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Alessandra Mocali ◽  
Nunzia Della Malva ◽  
Claudia Abete ◽  
Vito Antonio Mitidieri Costanza ◽  
Antonio Bavazzano ◽  
...  
Keyword(s):  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Low Cost ◽  
Apoe Genotype ◽  
Normal Subjects ◽  
Culture Conditions ◽  
Cultured Fibroblasts ◽  
Laboratory Tool

There is great interest in developing reliable biomarkers to support antemortem diagnosis of late-onset Alzheimer’s disease (AD). Early prediction and diagnosis of AD might be improved by the detection of a proteolytic dysfunction in extracts from cultured AD fibroblasts, producing altered isoelectrophoretic forms of the enzyme transketolase (TK-alkaline bands). The TK profile and apolipoprotein E (APOE) genotype were examined in fibroblasts from 36 clinically diagnosed probable late-onset sporadic AD patients and 38 of their asymptomatic relatives, 29 elderly healthy individuals, 12 neurological non-AD patients, and 5 early-onset AD patients. TK alterations occurred in (i) several probable AD patients regardless of age-of-onset and severity of disease; (ii) all early-onset AD patients and APOEε4/4 carriers; and (iii) nearly half of asymptomatic AD relatives. Normal subjects and non-AD patients were all negative. Notably, culture conditions promoting TK alterations were also effective in increasing active BACE1 levels. Overall, the TK assay might represent a low-cost laboratory tool useful for supporting AD differential diagnosis and identifying asymptomatic subjects who are at greater risk of AD and who should enter a follow-up study. Moreover, the cultured fibroblasts were confirmed as a usefulin vitromodel for further studies on the pathogenetic process of AD.

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