Browsing by Subject "RELATIVES"

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  • Bauer, Witold; Veijola, Riitta; Lempainen, Johanna; Kiviniemi, Minna; Härkönen, Taina; Toppari, Jorma; Knip, Mikael; Gyenesei, Attila; Ilonen, Jorma (2019)
    Context: Children with initial autoantibodies to either insulin (IAA) or glutamic acid decarboxylase (GADA) differ in peak age of seroconversion and have different type 1 diabetes (T1D) risk gene associations, suggesting heterogeneity in the disease process. Objective: To compare the associations of age at seroconversion, HLA risk, and specificity of secondary autoantibodies with the progression of islet autoimmunity between children with either IAA or GADA as their first autoantibody. Design and methods: A cohort of 15,253 children with HLA-associated increased risk of T1D participated in a follow-up program in which islet autoantibodies were regularly measured. The median follow-up time was 6.7 years. Spearman correlation, Kaplan-Meier survival plots, and Cox proportional-hazard models were used for statistical analyses. Results: Persistent positivity for at least one of the tested autoantibodies was detected in 998 children; 388 of children progressed to clinical T1D. Young age at initial seroconversion was associated with a high probability of expansion of IAA-initiated autoimmunity and progression to clinical diabetes, whereas expansion of GADA-initiated autoimmunity and progression to diabetes were not dependent on initial seroconversion age. The strength of HLA risk affected the progression of both IAA- and GADA-initiated autoimmunity. The simultaneous appearance of two other autoantibodies increased the rate of progression to diabetes compared with that of a single secondary autoantibody among subjects with GADA-initiated autoimmunity but not among those with IAA as the first autoantibody. Conclusions: Findings emphasize the differences in the course of islet autoimmunity initiated by either IAA or GADA supporting heterogeneity in the pathogenic process.
  • Virtanen, Suvi; Sidorchuck, Anna; Fernández de la Cruz, Lorena; Brander, Gustaf; Lichtenstein, Paul; Latvala, Antti; Mataix-Cols, David (2021)
    BACKGROUND: It remains unclear if individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) have an elevated risk of subsequent substance misuse. METHODS: In this population-based cohort study, we investigated the association between ICD diagnoses of TS/CTD and substance misuse outcomes, accounting for psychiatric comorbidity and familial factors. The cohort included all individuals living in Sweden at any time between January 1, 1973, and December 31, 2013. Substance misuse outcomes were defined as an ICD code of substance use-related disorder or cause of death, or as a substance use-related criminal conviction in the nationwide registers. RESULTS: The cohort included 14,277,199 individuals, of whom 7832 had a TS/CTD diagnosis (76.3% men). TS/CTD was associated with an increased risk of any subsequent substance misuse outcomes (adjusted hazard ratio [aHR], 3.11; 95% confidence interval [CI], 2.94-3.29), including alcohol-related disorder (aHR, 3.45; 95% CI, 3.19-3.72), drug-related disorder (aHR, 6.84; 95% CI, 6.32-7.40), substance-related criminal convictions (aHR, 2.56; 95% CI, 2.36-2.77), and substance-related death (aHR, 2.54; 95% CI, 1.83-3.52). Excluding psychiatric comorbidities had little effect on the magnitude of the associations, with the exception of attention-deficit/hyperactivity disorder, which attenuated the risk of any substance misuse outcomes (aHR, 2.00; 95% CI, 1.82-2.19). The risk of any substance misuse outcomes in individuals with TS/CTD was substantially attenuated but remained significant when compared with their unaffected siblings (aHR, 1.74; 95% CI, 1.53-1.97). CONCLUSIONS: TS/CTD were associated with various types of subsequent substance misuse outcomes, independently of psychiatric comorbidity and familial factors shared between siblings. Screening for drug and alcohol use should become part of the standard clinical routines, particularly in patients with comorbid attention-deficit/hyperactivity disorder.
  • Airaksinen, Laura; Myllymaki, Lauri; Kaukinen, Katri; Saavalainen, Päivi; Huhtala, Heini; Lindfors, Katri; Kurppa, Kalle (2021)
    Background It is not known if genetic background, characteristics at diagnosis, physical and psychological well-being, and adherence to a gluten-free diet are comparable between patients with familial or sporadic celiac disease. These issues were investigated in a follow-up study. Methods Altogether 1064 patients were analyzed for celiac disease-associated serology, predisposing HLA-DQ, and non-HLA genotypes. Medical data were collected from patient records and supplementary interviews. Current symptoms and quality of life were further evaluated with the Gastrointestinal Symptom Rating Scale (GSRS), the Psychological General Well-Being questionnaire (PGWB), and Short Form 36 (SF-36) questionnaires. Results Familial and sporadic groups differed (P <0.001) in the reason for diagnosis and clinical presentation at diagnosis, familial patients being more often screen-detected (26% vs. 2%,P <0.001) and having less often gastrointestinal (49% vs. 69%) and severe symptoms (47% vs. 65%). The groups were comparable in terms of histological damage, frequency of malabsorption, comorbidities, childhood diagnoses, and short-term treatment response. At the time of the study, familial cases reported fewer symptoms (21% vs. 30%,P = 0.004) and lower prevalence of all (78% vs. 86%,P = 0.007), neurological (10% vs. 15%,P = 0.013), and dermatological (9% vs. 17%,P = 0.001) comorbidities. Dietary adherence and GSRS scores were comparable, but familial cases had better quality of life according to PGWB and SF-36. High-risk genotype HLA-DQ2.5/DQ2.5 was more frequent among familial cases, and four non-HLA SNPs were associated with familial celiac disease. Conclusions Despite the greater proportion of high-risk genotypes, familial cases had milder symptoms at presentation than did sporadic cases. Worse experience of symptoms and poorer quality of life in sporadic disease indicate a need for intensified support.
  • Pöllänen, Petra M.; Ryhänen, Samppa J.; Toppari, Jorma; Ilonen, Jorma; Vähäsalo, Paula; Veijola, Riitta; Siljander, Heli; Knip, Mikael (2020)
    Context: We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context. Design: HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9-15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D. Results: By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3-15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschool years IA-2A- and especially GADA-initiated autoimmunity increased. Thereafter, GADA-positive seroconversions continued to appear steadily until ages 10 to 15 years. Inverse IAA seroconversions occurred frequently (49.3% turned negative) and marked a prolonged delay from seroconversion to diagnosis compared to persistent IAA (8.2 vs 3.4 years; P = .01). Conclusions: In HLA-predisposed children, the primary autoantibody is characteristic of age and might reflect the events driving the disease process toward clinical T1D. Autoantibody persistence affects the risk of T1D. These findings provide a framework for identifying disease subpopulations and for personalizing the efforts to predict and prevent T1D.
  • Zhang, Luyao; Yu, Hongyao; Hemminki, Otto; Försti, Asta; Sundquist, Kristina; Hemminki, Kari (2018)
    Familial risks for testicular cancer (TC) are among the highest of all cancers. However, data are limited for histological types of TC and for possible familial associations of TC with other cancers. We used the nationwide Swedish Family-Cancer Database for years 1958 to 2015 to analyse familial relative risks (RR) for 11,138 TC patients when first-degree relatives were diagnosed with TC or other cancer in reference to those without a family history. A total of 191 familial TCs were found, which accounted for 2.0% of all TC. The RR was 5.06 when one family member was diagnosed with TC with no significant difference between seminoma and nonseminoma. However, the risk for nonseminoma was 33.59 when two family members were affected. Internally consistent familial associations of TC, particularly of seminoma, were found with breast and nervous system cancers and melanoma. Individual significant associations were found for a number of sites, including ovarian, endometrial and prostate cancers. Our results suggest that nonseminoma may have a stronger genetic background than seminoma but seminoma shares more familial associations with discordant cancers. Clustering of TC with hormone-dependent cancers of the breast, ovary, endometrium and prostate may suggest mechanistic links and possibly gene-environment interactions.
  • Koskinen, Maarit K.; Helminen, Olli; Matomaki, Jaakko; Aspholm, Susanna; Mykkanen, Juha; Makinen, Marjaana; Simell, Ville; Vaha-Makila, Mari; Simell, Tuula; Ilonen, Jorma; Knip, Mikael; Veijola, Riitta; Toppari, Jorma; Simell, Olli (2016)
    Objective: We aimed to characterize insulin responses to i.v. glucose during the preclinical period of type 1 diabetes starting from the emergence of islet autoimmunity. Design and methods: A large population-based cohort of children with HLA-conferred susceptibility to type 1 diabetes was observed from birth. During regular follow-up visits islet autoantibodies were analysed. We compared markers of glucose metabolism in sequential intravenous glucose tolerance tests between 210 children who were positive for multiple (>= 2) islet autoantibodies and progressed to type 1 diabetes (progressors) and 192 children testing positive for classical islet-cell antibodies only and remained healthy (non-progressors). Results: In the progressors, the first phase insulin response (FPIR) was decreased as early as 4-6 years before the diagnosis when compared to the non-progressors (P=0.001). The difference in FPIR between the progressors and non-progressors was significant (P Conclusions: FPIR is decreased several years before the diagnosis of type 1 diabetes, implying an intrinsic defect in beta-cell mass and/or function.
  • Kauma, Saana; Kaukinen, Katri; Huhtala, Heini; Kivelä, Laura; Pekki, Henna; Salmi, Teea; Saavalainen, Päivi; Lindfors, Katri; Kurppa, Kalle (2019)
    The factors determining the presentation of celiac disease are unclear. We investigated the phenotypic concordance and the distribution of human leukocyte antigen (HLA) risk haplotypes in affected siblings. One hundred sibling pairs were included. Clinical and histological parameters and HLA haplotypes were compared between the first diagnosed indexes and their siblings. The phenotype was categorized into gastrointestinal, extra-intestinal, malabsorption/anemia, and asymptomatic. The phenotype was fully concordant in 21 pairs. The most common concordant phenotype was gastrointestinal (14 pairs). Indexes had more anemia/malabsorption and extra-intestinal symptoms than siblings (45% vs. 20%, p <0.001 and 33% vs. 12%, p <0.001, respectively). Twenty siblings and none of the indexes were asymptomatic. The indexes were more often women (81% vs. 63%, p = 0.008). They were also more often seronegative (11% vs. 0%, p = 0.03) and younger (37 vs. 43 year, p <0.001), and had more severe histopathology (total/subtotal atrophy 79% vs. 58%, p = 0.047) at diagnosis. The indexes and siblings were comparable in other disease features. Pairs with discordant presentation had similar HLA haplotypes more often than the concordant pairs. The phenotype was observed to vary markedly between siblings, with the indexes generally having a more severe presentation. HLA did not explain the differences, suggesting that non-HLA genes and environmental factors play significant roles.
  • Edgren, Robert; Pörtfors, Pia; Raisamo, Susanna; Castren, Sari (2022)
    Background and aims: Research recognizes the extent of harm experienced by concerned significant others (CSOs) of gamblers. This systematic review's aims are to examine the interventions for CSOs, evaluate potential benefits, and thematically describe treatment processes. The Stress-Strain-Coping-Support model (SSCS) served as the theoretical framework. Methods: Database searches were conducted in: MEDLINE, CINAHL Complete, Web of Science Core Collection, Social Services Abstracts, Applied Social Science Index and Abstracts, Cochrane Central Register of Controlled Trials, and APA Psyclnfo (between 01/Jan 2011-10/Jun 2021). Other search methods were also utilized. Inclusion criteria: interventions for CSOs with CSO specific outcomes. The Evidence Project Risk of Bias Tool was used for assessment. Results: 19/768 records were included. Nine interventions were utilized: 3 CSO directed, 4 for couples, and 2 low threshold online interventions. A quantitative synthesis (N = 7 studies) of effect size estimates for depression and anxiety measures didn't indicate any intervention to have better outcomes than others. Core themes in the treatment process identified in the qualitative synthesis (N = 7) included: information and understanding, social support, coping skills, communication, and strain. Limitations in the evidence related to sampling, control-conditions and outcome measurements. Discussion and conclusion: Several interventions were identified, yet no specific interventions appeared more beneficial than others. Using the SSCS model, commonalities and differences in intervention content were identified, along with themes that influence treatment processes. The need for tailored interventions is discussed. Future treatment efficacy research should carefully select study designs and outcome measurements.