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- Hakkinen, K, et al.
(författare)
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Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder
- 2022
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Ingår i: The pharmacogenomics journal. - : Springer Science and Business Media LLC. - 1473-1150 .- 1470-269X. ; 22:3, s. 166-172
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.
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- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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- Toimela, J.S., et al.
(författare)
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Association of obesity to reaction time and visual memory in schizophrenia
- 2024
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Ingår i: Schizophrenia Research. - : Elsevier. - 2215-0013. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both overweight and cognitive deficits are common among people with schizophrenia (SZ) and schizoaffective disorder. The results in earlier studies have been inconsistent on whether overweight is associated with cognitive deficits in psychotic disorders.Aims: Our aim in this study was to detect possible associations between obesity and cognitive deficits among study participants with SZ and schizoaffective disorder.Methods: The study sample included 5382 participants with a clinical diagnosis of SZ or schizoaffective disorder selected from the Finnish SUPER study. Obesity was measured both with body-mass index and waist circumference. The cognitive performance was evaluated with two tests from the Cambridge automated neuropsychological test battery: Reaction time was evaluated with the 5-choice serial reaction time task. Visual memory was evaluated with the paired associative learning test. The final analysis included a total sample of 4498 participants applicable for the analysis of the reaction time and 3967 participants for the analysis of the visual memory.Results: Obesity measured with body-mass index was associated with better performance in reaction time task among both female and male participants. Among male participants, overweight was associated with better performance in the visual memory test. The waist circumference was not associated with cognitive measures.Conclusions: The results suggest that obesity in people with SZ or schizoaffective disorder might not be associated with cognitive deficits but instead with better cognitive performance. The results were opposite from earlier literature on the general population. More research is required to better understand whether the results might be partly caused by the differences in the etiology of obesity between the general population and people with SZ.
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- Hakola, L., et al.
(författare)
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Maternal fatty acid intake during pregnancy and the development of childhood overweight : a birth cohort study
- 2017
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Ingår i: Pediatric Obesity. - : WILEY. - 2047-6302 .- 2047-6310. ; 12, s. 26-37
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMaternal diet during pregnancy may contribute to the risk of offspring adiposity. ObjectivesThe objective of the study is to explore the associations between maternal antenatal dietary fatty acid intake and the risk of offspring overweight and obesity at the ages of 2 to 7years. MethodsIn a prospective Finnish birth cohort with 3807 mother-child pairs, maternal diet in late pregnancy was assessed with a food frequency questionnaire. Intakes of total fatty acids and individual saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were calculated. Generalized estimating equation models were used to study the associations of maternal dietary variables with repeatedly measured offspring overweight and obesity. ResultsIn girls, maternal intake ratio of n-6:n-3 PUFAs had a U-shaped association with obesity (adjusted OR for the lowest 2.0 [95% CI 1.27-3.20] and the highest 1.7 [1.03-2.73] vs. the two middle quartiles of n-6:n-3 PUFAs, p=0.01). In boys, arachidonic acid (20:4n-6): docosahexaenoic acid+eicosapentaenoic acid ratio was associated with obesity (adjusted OR for the lowest 1.0 [0.60-1.57] and the highest 0.5 [0.26-0.88] vs. the two middle quartiles, p=0.02). Saturated fatty acids and monounsaturated fatty acids were not associated with overweight or obesity in either sex. ConclusionsMaternal intakes of PUFAs in late pregnancy were associated with risk of later obesity differently in girls and boys.
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- Protsenko, M, et al.
(författare)
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Mortality by diseases and medical conditions in the offspring of parents with severe mental illness
- 2020
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Ingår i: Social psychiatry and psychiatric epidemiology. - : Springer Science and Business Media LLC. - 1433-9285 .- 0933-7954. ; 55:212, s. 1649-1657
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe lifespan of people with severe mental illness (SMI) is shorter compared to the general population. There might be common familial pathway leading to a high co-occurrence of somatic disorders and SMI. To study this we explored the long-term mortality for natural causes in the offspring of people with SMI.MethodsParticipants were members of the Northern Finland Birth Cohort 1966 (NFBC1966;N = 11,325). The data on cause of deaths of the members were obtained from the Population Register Center until year 2015. The data on hospital-treated psychiatric disorders of parents were obtained from nationwide Care Register for Health Care. Cumulative incidences by age were calculated in the NFBC1966 members having a parent with SMI and those who did not have. We were able to take into account multiple confounders.ResultsOf the total sample of 11,325 offspring, 853 (7.4%) died during the follow-up period, 74 (8.7%) from the study cohort and 779 (91.3%) from the comparison group. These numbers included 160 stillborn children. There were 557 cases of deaths from diseases and medical conditions and 296 deaths from external causes. The adjusted risk ratio for offspring of mothers with SMI was 1.08 (0.72–1.64), and for offspring of fathers with SMI 0.58 (0.36–0.93).ConclusionsThis was the first long-term follow-up study (up to age 49) of all-cause mortality in offspring of parents with SMI. Our findings were contrary to expectations. Offspring of parents with SMI had no increased risk for dying. In fact, the risk for dying in the group of offspring of fathers with SMI was lower than in the comparison group. This study does not support the assumption of common familial pathway leading to a high co-occurrence of somatic disorders and SMI.
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- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 25. |
- Yang, J, et al.
(författare)
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Prevalence of obesity was related to HLA-DQ in 2-4-year-old children at genetic risk for type 1 diabetes.
- 2014
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 38:12, s. 1491-1496
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:Body size is postulated to modulate type 1 diabetes as either a trigger of islet autoimmunity or an accelerator to clinical onset after seroconversion. As overweight and obesity continue to rise among children, the aim of this study was to determine whether human leukocyte antigen DQ (HLA-DQ) genotypes may be related to body size among children genetically at risk for type 1 diabetes.Methods:Repeated measures of weight and height were collected from 5969 children 2-4 years of age enrolled in The Environmental Determinants of Diabetes in the Young prospective study. Overweight and obesity was determined by the International Obesity Task Force cutoff values that correspond to body mass index (BMI) of 25 and 30 kg m(-)(2) at age 18.Results:The average BMI was comparable across specific HLA genotypes at every age point. The proportion of overweight was not different by HLA, but percent obesity varied by age with a decreasing trend among DQ2/8 carriers (P for trend=0.0315). A multivariable regression model suggested DQ2/2 was associated with higher obesity risk at age 4 (odds ratio, 2.41; 95% confidence interval, 1.21-4.80) after adjusting for the development of islet autoantibody and/or type 1 diabetes.Conclusions:The HLA-DQ2/2 genotype may predispose to obesity among 2-4-year-old children with genetic risk for type 1 diabetes.International Journal of Obesity advance online publication, 29 April 2014; doi:10.1038/ijo.2014.55.
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