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- Weiner, D. J., et al.
(författare)
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Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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| 4. |
- Eyles, DW, et al.
(författare)
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The association between neonatal vitamin D status and risk of schizophrenia
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 17692-
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Tidskriftsartikel (refereegranskat)abstract
- Clues from the epidemiology of schizophrenia, such as the increased risk in those born in winter/spring, have led to the hypothesis that prenatal vitamin D deficiency may increase the risk of later schizophrenia. We wish to explore this hypothesis in a large Danish case-control study (n = 2602). The concentration of 25 hydroxyvitamin D (25OHD) was assessed from neonatal dried blood samples. Incidence rate ratios (IRR) were calculated when examined for quintiles of 25OHD concentration. In addition, we examined statistical models that combined 25OHD concentration and the schizophrenia polygenic risk score (PRS) in a sample that combined the new sample with a previous study (total n = 3464; samples assayed and genotyped between 2008-2013). Compared to the reference (fourth) quintile, those in the lowest quintile (<20.4 nmol/L) had a significantly increased risk of schizophrenia (IRR = 1.44, 95%CI: 1.12–1.85). None of the other quintile comparisons were significantly different. There was no significant interaction between 25OHD and the PRS. Neonatal vitamin D deficiency was associated with an increased risk for schizophrenia in later life. These findings could have important public health implications related to the primary prevention of schizophrenia.
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| 7. |
- Jorgensen, F S, et al.
(författare)
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MULTISCAN--a Scandinavian multicenter second trimester obstetric ultrasound and serum screening study
- 1999
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 1600-0412. ; 78:6, s. 501-510
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the detection rates of second trimester ultrasound screening for neural tube defects (NTD), abdominal wall defects (AWD) and Down's syndrome (DS) in low risk populations at tertiary centers, and to compare the ultrasound screening detection rates with those that were obtainable by biochemical serum screening (double test: alpha-fetoprotein/human chorion gonadotrophin/age test). STUDY DESIGN: Prospective multicenter study with a three year inclusion period: 1/1/1989-31/12/1991. SUBJECTS: 27,844 low-risk women at 18-34 years of age who had a second trimester ultrasound screening examination. Of these, 10,264 also had a serum test. METHODS: An ultrasound malformation scan and a serum test were carried out at 17-19 weeks of gestation. Risk calculations regarding DS were based on alpha-fetoprotein, human chorion gonadotrophin and maternal age; performed retrospectively for the first two years. RESULTS: In total 73 cases were identified in the study population: NTD (n=34), AWD (n=7) and DS (n=32). The detection rates, (%, with 95% confidence interval) for ultrasound screening were: NTD: 79.4 (62.1-91.3); AWD: 85.7 (42.1-99.6); DS: 6.3 (0.8-20.8). In the subgroup of women who had both tests, the detection rates for ultrasound screening vs double test were: NTD: 62.5 (24.5-91.5) vs 75.0 (34.9-96.8); AWD: 66.7 (9.4-99.2) vs 100 (29.2-100.0); DS: 7.7 (0.2-36.0) vs 46.2 (19.2-74.9). The false positive rates (%) for ultrasound screening vs double test were: NTD: 0.01/3.3; AWD: 0.01/3.3; DS: 0.1/4.0. CONCLUSION: Second trimester ultrasound screening in a low risk population gave a low detection rate for fetal DS (6.3%) and an acceptable detection rate for NTD (79.4%) and AWD (85.7%). In the subgroup of women who had both tests, serum screening performed better than ultrasound as applied in the present study, especially regarding DS.
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| 10. |
- Skogstrand, K., et al.
(författare)
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Effects of blood sample handling procedures on measurable inflammatory markers in plasma, serum and dried blood spot samples
- 2008
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Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 0022-1759. ; 336:1, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- The interests in monitoring inflammation by immunoassay determination of blood inflammatory markers call for information on the stability of these markers in relation to the handling of blood samples. The increasing use of stored biobank samples for such ventures that may have been collected and stored for other purposes, justifies the study hereof. Blood samples were stored for 0, 4, 24, and 48 h at 4 degrees C, room temperature (RT), and at 35 degrees C, respectively, before they were separated into serum or plasma and frozen. Dried blood spot samples (DBSS) were stored for 0, 1, 2, 3, 7, and 30 days at the same temperatures. 27 inflammatory markers in serum and plasma and 25 markers in DBSS were measured by a previously validated multiplex sandwich immunoassay using Luminex xMAP technology. The measurable concentrations of several cytokines in serum and plasma were significantly increased when blood samples were stored for a period of time before the centrifugation, for certain cytokines more than 1000 fold compared to serum and plasma isolated and frozen immediately after venepuncture. The concentrations in serum generally increased more than in plasma. The measurable concentrations of inflammatory markers also changed in DBSS stored under various conditions compared to controls frozen immediately after preparation, but to a much lesser degree than in plasma or serum. The study demonstrates that trustworthy measurement of several inflammatory markers relies on handling of whole blood samples at low temperatures and rapid isolation of plasma and serum. Effects of different handling procedures for all markers studied are given. DBSS proved to be a robust and convenient way to handle samples for immunoassay analysis of inflammatory markers in whole blood.
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