Publications by authors named "Teemu Kuulasmaa"
Aims: To investigate a comprehensive panel of biomarkers and risk of aortic stenosis (AS) in a prospective population-based study.
Methods: Anthropometric, metabolic, and inflammatory biomarkers were measured in the Metabolic Syndrome in the Men Study of 10,144 Finnish men without AS at baseline. Cases of AS were identified from the medical records.
Background And Objectives: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH).
Methods: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records.
Article Synopsis
- A lifestyle intervention can effectively lower the risk of developing type 2 diabetes (T2D) in individuals at high genetic risk, while the impact on those with low genetic risk is less clear.
- In a study involving 973 middle-aged men, participants were divided into groups based on genetic risk and received a three-year intervention focusing on diet and exercise.
- Findings indicated that the intervention significantly reduced T2D risk for those with high genetic risk, while it did not show a significant effect for the low-risk group, suggesting that lifestyle changes can be beneficial for high-risk individuals.
Article Synopsis
- A healthy placenta is crucial for both the mother and fetus during pregnancy, and this study uses placental weight as a measure of its growth.
- Genome-wide analyses across the genomes of mothers, fathers, and fetuses identified 40 genetic signals related to placental weight, revealing a mix of influences from both parents and the fetus.
- The findings suggest that higher placental weight, driven by fetal genetics, is linked to an increased risk of preeclampsia and shorter pregnancy duration, highlighting the role of fetal insulin in regulating placental growth.
Article Synopsis
- Scientists studied over 176,000 people to see how certain genes might protect against Parkinson's disease (PD) and Alzheimer's disease (AD).
- They found that specific types of a gene called HLA could help reduce the risk of these diseases and lower harmful proteins in the brain.
- This suggests that our immune system might help protect us from PD and AD, which could lead to new treatments in the future.
Article Synopsis
- An estimated 40% of dementia cases might be preventable by altering 12 specific risk factors throughout a person's life, although there's insufficient evidence for many of them.
- The study aims to identify causal relationships between modifiable risk factors for Alzheimer’s disease (AD) to encourage new treatment options and better prevention strategies.
- Researchers analyzed data from over 39,000 AD patients and 401,000 controls, finding that higher genetically determined levels of HDL cholesterol and systolic blood pressure were linked to an increased risk of developing AD.
Article Synopsis
- * Researchers utilized mass spectrometry to analyze cerebrospinal fluid and plasma from both A673T carriers and non-carriers, revealing significant decreases in soluble APPβ and amyloid beta levels in carriers.
- * In cell culture studies, the A673T variant showed the potential to lower harmful proteins associated with Alzheimer's, suggesting its important role in mitigating AD-related pathology.
Article Synopsis
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) offer better insight into Alzheimer's disease (AD) than just clinical diagnosis.
- The European Alzheimer & Dementia Biobank (EADB) analyzed data from 31 cohorts with over 13,000 individuals, identifying new genetic associations such as CR1 for Aβ42 and BIN1 for pTau, alongside novel associations with GMNC and C16orf95.
- Analysis of all AD risk loci revealed four biological categories linked to Aβ42 and pTau, suggesting multiple pathways in AD's development, with further studies indicating GMNC and C16orf95 also relate to brain ventricular volume.
Article Synopsis
- The APOE ε2 and ε4 alleles are well-known genetic variants linked to Alzheimer’s Disease (AD), but the specific roles of apoE protein and rare genetic variants in AD risk are not fully understood.
- The study aims to find connections between rare missense variants in the APOE gene and the risk of developing AD.
- It involved analyzing a large sample of participants across multiple cohorts, including a significant number with and without AD, to assess the relationship between these variants and AD risk through established statistical methods.
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.
View Article and Find Full Text PDFBackground: C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exp requires elaborative methods.
Objective: Identification of C9exp carriers from genotyped cohorts could be facilitated by using single nucleotide polymorphisms (SNPs) as markers for the C9exp.
Background And Aims: To investigate the significance of 9 amino acids as risk factors for incident cardiovascular disease events in 9584 Finnish men.
Materials And Methods: A total of 9584 men (age 57.4 ± 7.
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene).
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- Scientists studied people's genetics to learn about traits related to blood sugar, which helps diagnose and monitor type 2 diabetes.
- Most of the earlier studies only looked at people with European backgrounds, but this research included many more individuals from different backgrounds, finding 242 important genetic spots linked to blood sugar levels.
- By studying a diverse group of people, they discovered new insights about how diabetes works in the body, helping to uncover different biological processes for each glycemic trait.
Methyl-CpG-binding protein 2 (MECP2) is a critical transcriptional regulator for synaptic function. Dysfunction of synapses, as well as microglia-mediated neuroinflammation, represent the earliest pathological events in Alzheimer's disease (AD). Here, expression, protein levels, and activity-related phosphorylation changes of MECP2 were analyzed in post-mortem human temporal cortex.
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- Isoflurane, a widely used anesthetic, causes long-lasting changes in brain function and behavior, likely due to altered neural connectivity.
- In a study with male Wistar rats, a three-hour exposure to isoflurane led to strengthened connections in thalamo-cortical and hippocampal-cortical networks, as measured by fMRI and electrical recordings.
- Additionally, gene expression analysis revealed changes in 20 cortical genes related to neuronal signaling, but no changes in the hippocampus, suggesting that isoflurane has a prolonged impact on cortical function and gene activity.
Aims: There are only a few studies on novel biomarkers for incident heart failure (HF). We investigated the association of multiple circulating biomarkers with incident HF in a large prospective population-based study.
Methods And Results: Conventional risk factors and inflammatory biomarkers were measured, and systemic metabolic measures determined by a high-throughput serum nuclear magnetic resonance platform in a population-based Metabolic Syndrome in Men study including 10 106 Finnish men without HF at baseline.
Idiopathic normal pressure hydrocephalus (iNPH) is characterized clinically by degradation of gait, cognition, and urinary continence. INPH is progressive (Andrén et al, 2014), still probably underdiagnosed (Williams et al, 2019) but potentially treatable by CSF diversion (Kazui et al, 2015). Familial aggregation is a strong indicator of genetic regulation in the disease process iNPH (Fig 1).
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most common neurodegenerative disease and type 2 diabetes (T2D) plays an important role in conferring the risk for AD. Although AD and T2D share common features, the common molecular mechanisms underlying these two diseases remain elusive.
Methods: Mice with different AD- and/or tauopathy-linked genetic backgrounds (APPswe/PS1dE9, Tau P301L and APPswe/PS1dE9/Tau P301L) were fed for 6 months with standard diet or typical Western diet (TWD).
Article Synopsis
- - The study identifies a rare genetic variant (PLCG2-P522R) linked to reduced risk for Alzheimer’s disease (AD) and investigates its role in immune cell functions through a genetically modified mouse model.
- - The PLCG2-P522R variant enhances macrophage functions, such as improved survival and inflammation response, and increases phagocytosis in microglia-like cells, suggesting enhanced microglial activity in the genetically modified mice.
- - The findings suggest that the PLCG2-P522R variant may promote protective immune responses in the brain via TREM2 signaling, highlighting its potential as a target for new AD therapies.
Objective: Recent studies have highlighted the significance of the microbiome in human health and disease. Changes in the metabolites produced by microbiota have been implicated in several diseases. Our objective was to identify microbiome metabolites that are associated with type 2 diabetes.
View Article and Find Full Text PDFContext: Major advances have been made in the genetics and classification of congenital hyperinsulinism (CHI).
Objective: To examine the genetics and clinical characteristics of patients with persistent and transient CHI.
Design: A cross-sectional study with the register data and targeted sequencing of 104 genes affecting glucose metabolism.
Previous studies have shown that an intronic variant rs780094 of the GCKR gene (glucokinase regulatory protein) is significantly associated with several metabolites, but the associations of this genetic variant with different lipids is largely unknown. Therefore, we applied metabolomics approach to measure metabolites in a large Finnish population sample (METSIM study) to investigate their associations with rs780094 of GCKR. We measured metabolites by mass spectrometry from 5,181 participants.
View Article and Find Full Text PDFAims: Nationwide large-scale genetic and outcome studies in cohorts with hypertrophic cardiomyopathy (HCM) have not been previously published.
Methods And Results: We sequenced 59 cardiomyopathy-associated genes in 382 unrelated Finnish patients with HCM and found 24 pathogenic or likely pathogenic mutations in six genes in 38.2% of patients.