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- Witt, S. H., et al.
(författare)
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Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia
- 2017
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P = 4.42 x 10(-7)) and PKP4 (P = 8.67 x 10(-7)); and gene-set analysis yielded a significant finding for exocytosis (GO: 0006887, PFDR = 0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r(g) = 0.28 [P = 2.99 x 10(-3)]), SCZ (r(g) = 0.34 [P = 4.37 x 10(-5)]) and MDD (r(g) = 0.57 [P = 1.04 x 10(-3)]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
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| 5. |
- Hvidtjorn, D., et al.
(författare)
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Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis
- 2009
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Ingår i: Arch Pediatr Adolesc Med. ; 163:1, s. 72-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay. DATA SOURCES: Forty-one studies identified in a systematical PubMed and Excerpta Medica Database (EMBASE) search for articles published from January 1, 1996, to April 1, 2008. STUDY SELECTION: Studies written in English comparing children born after assisted conception with children born after natural conception assessing CP, ASD, and developmental delay, based on original data with a follow-up of 1 year or more. Main Exposures In vitro fertilization (IVF) with or without intracytoplasmic sperm injection or ovulation induction with or without subsequent intrauterine insemination. MAIN OUTCOME MEASURES: Cerebral palsy, ASD, and developmental delay. RESULTS: Nine CP studies showed that children born after IVF had an increased risk of CP associated with preterm delivery. In our meta-analysis including 19 462 children exposed to IVF, we estimated a crude odds ratio of 2.18 (95% confidence interval, 1.71-2.77). Eight ASD studies and 30 studies on developmental delay showed inconsistent results. No studies assessed the risk of CP, ASD, or developmental delay in children born after ovulation induction exclusively. CONCLUSIONS: Methodological problems were revealed in the identified studies, and the gaps in our knowledge about the long-term outcomes of children born after assisted conception are considerable, including a lack of information on the long-term consequences of ovulation induction. Possible associations with ASD and developmental delay need assessment in larger studies. Studies on assisted conception and CP from countries outside of Scandinavia are needed, including detailed information on time to pregnancy, underlying cause of infertility, and type of IVF treatment.
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| 6. |
- Hvidtjørn, D, et al.
(författare)
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Multiplicity and early gestational age contribute to an increased risk of cerebral palsy from assisted conception: a population-based cohort study.
- 2010
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 25:8, s. 2115-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This paper assesses the risk of cerebral palsy (CP) in children born after assisted conception compared with children born after natural conception (NC). METHODS: This population based follow-up study included all 588,967 children born in Denmark from 1995 to 2003. Assisted conception was defined as IVF, with or without ICSI, and ovulation induction (OI), with or without subsequent insemination. RESULTS: There were 33 139 (5.6%) children born in Denmark from 1995 to 2003 as a result of assisted conception and through to June 2009, 1146 (0.19%) children received a CP diagnosis. Children born after assisted conception had an increased risk of a CP diagnosis, crude hazard rate ratio (HRR) 1.90 (95% CI: 1.57-2.31) compared with NC children. Divided into IVF and OI children compared with NC children, the risk was HRR 2.34 (95% CI: 1.81-3.01) and HRR 1.55 (95% CI: 1.17-2.06), respectively. When we included the intermediate factors multiplicity and gestational age in multivariate models, the risk of CP in assisted conception disappeared. In general, children with CP born after assisted conception had similar CP subtypes and co-morbidities as children with CP born after NC. CONCLUSION: The risk of CP is increased after both IVF and OI. The increased risk of CP in children born after assisted conception, and in particular IVF, is strongly associated with the high proportion of multiplicity and preterm delivery in these pregnancies. A more widespread use of single embryo transfer warrants consideration to enhance the long-term health of children born after IVF.
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| 7. |
- Nielsen, L. F., et al.
(författare)
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Asphyxia-related risk factors and their timing in spastic cerebral palsy
- 2008
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Ingår i: BJOG. - : Wiley. - 1471-0528. ; 115:12, s. 1518-28
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the association of asphyxia-related conditions (reducing blood flow or blood oxygen levels in the fetus) with spastic cerebral palsy (CP) considering different gestational age groups and the timing of risk. DESIGN: Population-based case-control study. SETTING: Danish Cerebral Palsy Register in eastern Denmark and Danish Medical Birth Register. POPULATION OR SAMPLE: 271 singletons with spastic CP and 217 singleton controls, frequency matched by gestational age group, born 1982-1990 in eastern Denmark. METHODS: Data were abstracted from medical records, and a priori asphyxia-related conditions and other risk factors were selected for analysis. Each factor was classified according to the time at which it was likely to first be present. MAIN OUTCOME MEASURES: Spastic CP. RESULTS: Placental and cord complications accounted for the majority of asphyxia conditions. In multivariate analysis, placental infarction was significantly associated with a four-fold increased risk for spastic quadriplegia and cord around the neck was significantly associated with a three-fold increased risk for spastic CP overall. The combination of placental infarction and being small for gestational age (SGA) afforded an especially high risk for spastic quadriplegia. Placental and cord complications were present in 21% of cases and 12% of controls. CONCLUSIONS: The risk for spastic quadriplegia from placental infarction may be linked in some cases with abnormal fetal growth (17% of all children with spastic quadriplegia and 3% of control children both had an infarction and were SGA) -- suggesting an aetiologic pathway that encompasses both factors. The risk for spastic CP from cord around the neck is not accounted for by other prepartum or intrapartum factors we examined. Considering the relative timing of risk factors provides a useful framework for studies of CP aetiology.
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- Braun, M, et al.
(författare)
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The CD6 scavenger receptor is differentially expressed on a CD56 natural killer cell subpopulation and contributes to natural killer-derived cytokine and chemokine secretion
- 2011
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 3:4, s. 420-434
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Tidskriftsartikel (refereegranskat)abstract
- The CD6 scavenger receptor is known to be expressed on virtually all T cells and is supposed to be involved in costimulation, synapse formation, thymic selection and leukocyte migration. Here, we demonstrate that CD6 is differentially expressed by a subpopulation of peripheral CD56<sup>dim</sup> natu- ral killer (NK) cells and absent on CD56<sup>bright</sup> NK cells. CD56<sup>dim</sup>CD16<sup>+</sup> cells represent the major NK subset in the periphery, and most cells within this group are positive for CD6. Most killer immunoglobulin-like receptor- and immunoglobulin-like transcript-positive cells also belong to the CD6<sup>+</sup> subpopulation, as expected from their restricted expression on CD56<sup>dim</sup> NK cells. In addition, CD6<sup>+</sup> NK cells are similar to the newly identified CD94<sup>low</sup>CD56<sup>dim</sup> NK subpopulation and most distant from the recently defined CD27<sup>+</sup> NK subpopulation based on the reverse correlation of expression between CD6 and CD27, a marker associated primarily with CD56<sup>bright</sup> NK cells. With respect to CD6 function on NK cells, direct CD6 triggering did not result in degranulation but induced secretion of cytokines (interferon-γ and tumor necrosis factor-α) and chemokines [CXCL10 (IP-10), CXCL1 (GRO-α)]. Thus, CD6 expression on peripheral NK cells marks a novel CD56<sup>dim</sup> subpopulation associated with distinct patterns of cytokine and chemokine secretion.
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