Browsing by Subject "genetic risk"

Sort by: Order: Results:

Now showing items 1-5 of 5
  • Lokki, A. Inkeri; Kaartokallio, Tea; Holmberg, Ville; Onkamo, Paivi; Koskinen, Lotta L. E.; Saavalainen, Paivi; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Villa, Pia M.; Hiltunen, Leena; Laivuori, Hannele; Meri, Seppo (2017)
    Preeclampsia (PE) is a common vascular disease of pregnancy with genetic predisposition. Dysregulation of the complement system has been implicated, but molecular mechanisms are incompletely understood. In this study, we determined the potential linkage of severe PE to the most central complement gene, C3. Three cohorts of Finnish patients and controls were recruited for a genetic case-control study. Participants were genotyped using Sequenom genotyping and Sanger sequencing. Initially, we studied 259 Finnish patients with severe PE and 426 controls from the Southern Finland PE and the Finnish population-based PE cohorts. We used a custom-made single nucleotide polymorphism (SNP) genotyping assay consisting of 98 SNPs in 18 genes that encode components of the complement system. Following the primary screening, C3 was selected as the candidate gene and consequently Sanger sequenced. Fourteen SNPs from C3 were also genotyped by a Sequenom panel in 960 patients with severe PE and 705 controls, including already sequenced individuals. Three of the 43 SNPs observed within C3 were associated with severe PE: rs2287845 (p = 0.038, OR = 1.158), rs366510 (p = 0.039, OR = 1.158), and rs2287848 (p = 0.041, OR = 1.155). We also discovered 16 SNP haplotypes with extreme linkage disequilibrium in the middle of the gene with a protective (p = 0.044, OR = 0.628) or a predisposing (p = 0.011, OR = 2.110) effect to severe PE depending on the allele combination. Genetic variants associated with PE are located in key domains of C3 and could thereby influence the function of C3. This is, as far as we are aware, the first candidate gene in the complement system with an association to a clinically relevant PE subphenotype, severe PE. The result highlights a potential role for the complement system in the pathogenesis of PE and may help in defining prognostic and therapeutic subgroups of preeclamptic women.
  • Komulainen, K; Pulkki-Raback, L; Jokela, M; Lyytikäinen, LP; Pitkänen, N; Laitinen, T; Hintsanen, M; Elovainio, M; Hintsa, T; Jula, A (2018)
    Objectives:The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI.Subjects/Methods:The study comprised 2441 participants (1319 women, 3-18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m 2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood.Results:Mean BMI increased from 22.6 to 26.6 kg/m 2 during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01-0.02, P
  • Kuusela, Salla; Keskinen, Päivi; Pokka, Tytti; Knip, Mikael; Ilonen, Jorma; Vähäsalo, Paula; Veijola, Riitta (2020)
    Objective The aim of this study was to explore the extended family history of type 1 diabetes in children at genetic risk and define the impact of a positive family history on the development of islet autoimmunity and type 1 diabetes. Methods The subjects were participants in The Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study and carried increased HLA-conferred risk for type 1 diabetes. The case children (N = 343) were positive for at least one islet autoantibody, and the control children (N = 343) matched by age, gender and class II HLA genotype were negative for islet autoantibodies at the time of data collection. Extended family history of type 1 diabetes was obtained by using a structured questionnaire. Results Among children who were autoantibody positive and progressed to type 1 diabetes 62.2% (28/45) had at least one relative with type 1 diabetes. Interestingly, 57.8% of these children (26/45) had such a relative outside the nuclear family compared to 30.7% of children with no autoantibodies (P= .001), 35.2% of those with only classical islet cell antibodies (P= .006), and 35.2% of non-progressors with biochemical autoantibodies (P= 0.011). A positive history of type 1 diabetes in the paternal extended family was more common in children with multiple biochemical autoantibodies compared to those with only one biochemical autoantibody (P= .010). No association between the specificity of the first appearing autoantibody and family history of the disease was found. Conclusions Type 1 diabetes in relatives outside the nuclear family is a significant risk factor for islet autoimmunity and progression to clinical disease in HLA susceptible children.
  • Morales-Munoz, Isabel; Kantojärvi, Katri; Uhre, Veli-Matti; Saarenpää-Heikkilä, Outi; Kylliäinen, Anneli; Pölkki, Pirjo; Himanen, Sari-Leena; Karlsson, Linnea; Karlsson, Hasse; Paavonen, E. Juulia; Paunio, Tiina (2021)
    Purpose: No previous research has examined the impact of the genetic background of diurnal preference on children´s sleep. Here, we examined the effects of genetic risk score for the liability of diurnal preference on sleep development in early childhood in two population-based cohorts from Finland. Participants and methods: The primary sample (CHILD-SLEEP, CS) comprised 1420 infants (695 girls), and the replication sample (FinnBrain, FB; 962 girls) 2063 infants. Parent-reported sleep duration, sleep-onset latency and bedtime were assessed at three, eight, 18 and 24 months in CS, and at six, 12 and 24 months in FB. Actigraphy-based sleep latency and efficiency were measured in CS in 365 infants at eight months (168 girls), and in 197 infants at 24 months (82 girls). Mean standard scores for each sleep domain were calculated in both samples. Polygenic risk scores (PRS) were used to quantitate the genetic risk for eveningness (PRSBestFit) and morningness (PRS10kBest). Results: PRSBestFit associated with longer sleep-onset latency and later bedtime, and PRS10kBest related to shorter sleep-onset latency in CS. The link between genetic risk for diurnal preference and sleep-onset latency was replicated in FB, and meta-analysis resulted in associations (P<0.0005) with both PRS-values (PRSBestFit: Z=3.55; and PRS10kBest: Z=-3.68). Finally, PRSBestFit was related to actigraphy-based lower sleep efficiency and longer sleep latency at eight months. Conclusion: Genetic liability to diurnal preference for eveningness relates to longer sleep-onset during the first two years of life, and to objectively measured lowered sleep efficiency. These findings enhance our understanding on the biological factors affecting sleep development, and contribute to clarify the physiological sleep architecture in early childhood.
  • Snell, Karoliina; Helén, Ilpo (2020)
    This article presents results from a Finnish focus group's study conducted among participants of a project called GeneRISK, in which the participants received a personal risk score for having a cardiovascular event based on genetic analysis, lifestyle and laboratory results. In the discussions, interpretations of the genetic risk score and its meaning were incorporated into personal narratives of health and illness. We argue that instead of serving as an explanation for health and illness, which can help guide people's lives and choices, the genetic risk information became an object of explanation. Therefore, the risk information did not create new conceptions of personal risk, nor did it generate enough power to push people to change their lifestyles. Instead, the risk information was used to strengthen the existing impression of personal risk and the narrative of personal health and illness.