Browsing by Subject "APOE"

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  • FinnGen; Kurki, Samu N.; Kantonen, Jonas; Kaivola, Karri; Hokkanen, Laura; Mäyranpää, Mikko I.; Puttonen, Henri; Martola, Juha; Pöyhönen, Minna; Kero, Mia; Tuimala, Jarno; Carpen, Olli; Kantele, Anu; Vapalahti, Olli; Tiainen, Marjaana; Tienari, Pentti J.; Kaila, Kai; Hastbacka, Johanna; Myllykangas, Liisa (2021)
    Apolipoprotein E epsilon 4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.
  • Rantalainen, Ville; Lahti, Jari; Kajantie, Eero; Tienari, Pentti; Eriksson, Johan G.; Raikkonen, Katri (2019)
    We tested if the epsilon 4 major isoform of the APOE gene and rs405509 and rs440446 promoter and intron-1 polymorphisms predicted risk of any dementia or Alzheimer's disease with diagnoses derived from the Hospital Discharge and Causes of Death Registers in 1453 participants of the Helsinki Birth Cohort Study. We used Cox proportional hazard models adjusted for sex, year of birth, maximum lifetime occupational status and education, and diagnoses of stroke, coronary heart disease, mood disorders, and depressive symptoms. APOE epsilon 4 predicted higher risk of any dementia (hazard ratios >3.68; 95% confidence interval [CI] 1.76, 7.70) across all statistical models, and when adjusted for rs405509 and rs440446. The number of minor alleles in rs405509 or rs440446 was not associated with dementia risk (hazard ratios
  • Huovinen, Joel; Kastinen, Sami; Komulainen, Simo; Oinas, Minna; Avellan, Cecilia; Frantzen, Janek; Rinne, Jaakko; Ronkainen, Antti; Kauppinen, Mikko; Lonnrot, Kimmo; Perola, Markus; Pyykko, Okka T.; Koivisto, Anne M.; Remes, Anne M.; Soininen, Hilkka; Hiltunen, Mikko; Helisalmi, Seppo; Kurki, Mitja; Jaaskelainen, Juha E.; Leinonen, Ville (2016)
    Idiopathic normal pressure hydrocephalus (iNPH) is a late-onset surgically alleviated, progressive disease. We characterize a potential familial subgroup of iNPH in a nation-wide Finnish cohort of 375 shunt-operated iNPH-patients. The patients were questionnaired and phone-interviewed, whether they have relatives with either diagnosed iNPH or disease-related symptomatology. Then pedigrees of all families with more than one iNPH-case were drawn. Eighteen patients (4.8%) from 12 separate pedigrees had at least one shunt-operated relative whereas 42 patients (11%) had relatives with two or more triad symptoms. According to multivariate logistic regression analysis, familial iNPH-patients had up to 3-fold risk of clinical dementia compared to sporadic iNPH patients. This risk was independent from diagnosed Alzheimer's disease and APOE epsilon 4 genotype. This study describes a familial entity of iNPH offering a novel approach to discover the potential genetic characteristics of iNPH. Discovered pedigrees offer an intriguing opportunity to conduct longitudinal studies targeting potential preclinical signs of iNPH. (C) 2016 Elsevier B.V. All rights reserved.
  • Rinta-Kanto, Jenni (Helsingfors universitet, 2016)
    Background: Development of cognitive abilities involves both environmental and genetic factors. Childhood socioeconomic status (SES) associates with cognitive abilities later in life; however there is only little research on the interaction of SES and genes on cognitive ability. Specific genomic loci associating with cognitive abilities are scarce and potential candidates might be genetic variants linked with Alzheimer's disease such as APOE ε4 isomorph and rs405509 located in the APOE promoter region. I studied how childhood SES and APOE ε4 and rs405509 and their interactions associate with cognitive abilities in late adulthood in the Helsinki Birth Cohort Study (HBCS) sample. Methods: The participants of this study consisted of 607 men belonging to the HBCS who were born in Helsinki, Finland between 1934 and 1944. They participated in the test for general cognitive abilities at the average age of 68, and who were successfully genotyped. Associations and interactions of childhood SES, APOE and rs405509 on cognitive ability were studied. Results and conclusions: Lower childhood SES associated with lower verbal subscale score and total score. APOE ε4 was not independently associated with cognitive abilities. The number of G-alleles in rs405509 associated with lower verbal subscale score and total score when adjusted for age, but no longer after adjusting for adulthood SES. Interactions of rs405509 and childhood SES were not associated with cognitive ability. Socioeconomically less advantaged childhood environment has long-term consequences on cognitive abilities, and the effects last until late adulthood. The study suggests that rs405509 G-allele might have an independent effect on cognitive ability before the outset of Alzheimer's disease, but the results require further replication with larger sample size.
  • 23andMe Res Team; IPDGC; Blauwendraat, Cornelis; Heilbron, Karl; Vallerga, Costanza L.; Eerola-Rautio, Johanna; Tienari, Pentti; Singleton, Andrew B. (2019)
    Background Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age at onset are largely unknown. Objectives To identify the genetic determinants of PD age at onset. Methods Using genetic data of 28,568 PD cases, we performed a genome-wide association study based on PD age at onset. Results We estimated that the heritability of PD age at onset attributed to common genetic variation was similar to 0.11, lower than the overall heritability of risk for PD (similar to 0.27), likely, in part, because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni-corrected significant effect at other known PD risk loci, GBA, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. Notably, SNCA, TMEM175, SCARB2, BAG3, and GBA have all been shown to be implicated in alpha-synuclein aggregation pathways. Remarkably, other well-established PD risk loci, such as GCH1 and MAPT, did not show a significant effect on age at onset of PD. Conclusions Overall, we have performed the largest age at onset of PD genome-wide association studies to date, and our results show that not all PD risk loci influence age at onset with significant differences between risk alleles for age at onset. This provides a compelling picture, both within the context of functional characterization of disease-linked genetic variability and in defining differences between risk alleles for age at onset, or frank risk for disease. (c) 2019 International Parkinson and Movement Disorder Society
  • Silvo, Jenni (Helsingin yliopisto, 2018)
    Objectives: Low birth weight has been associated with impaired cognitive abilities especially in childhood and young adulthood. However, the role of a low Apgar score on cognitive functions remains unclear. Apoliprotein E (APOE) gene allele ε4 has been linked to older people’s cognition, but the influence of APOE alleles on cognition of children or middle-aged is not well understood. The present study investigated the effects of low birth weight (< 2000 g) and low Apgar scores (< 7) on later cognitive performance and on the stability of cognitive functions from childhood to middle age. In addition, the influence of APOE ε2 and ε4 alleles on risk group subjects’ cognitive performance was evaluated. It was hypothesized that the groups with perinatal risk factors have impaired cognitive abilities in all the domains and have lower stability within these abilities compared to controls. Low birth weight was hypothesized to contribute lower cognitive abilities more than a low Apgar score. It was also assumed that APOE ε4 allele impairs cognitive performance only at midlife, not in childhood. Methods: The subjects with low birth weight (n = 66) and/or a low Apgar score (n = 60) were selected from a birth cohort born during 1971–1974. The control subjects (n = 95) were free from perinatal risk factors. Cognitive performance was evaluated using Wechsler’s intelligence test. All the subjects completed the test at the age of 40 (n = 221) and some also at the age of 9 (n = 190). The differences between the groups were computed with the analysis of covariance, where family socioeconomic status was controlled. Differences in the stability of cognitive abilities were evaluated with repeated measures ANOVA and correlation analysis. The effect of APOE ε2 and ε4 alleles on cognitive performance was computed with t-test. Results and conclusions: The subjects with low birth weight reached lower scores in all the cognitive domains compared to controls. At midlife, there was also a trend towards lower general intelligence in individuals with a low Apgar score. The lowest stability in cognitive performance between childhood and middle-age was observed among those born with a low birth weight. However, the difference in the stability was not significant between the groups. APOE ε4 allele was related to lower ability of perceptual reasoning in childhood and middle age. According to the results, the effects of low birth weight on cognitive functions seem to extend to middle age. However, it is assumed that environmental factors have an important role in later development in people with low birth weight. Based on the results, the APOE ε4 allele might impact already on early cognitive development. In the future, it is important to examine if this initial impairment in perceptual reasoning is related to abnormal aging among those with APOE ε4 allele.