| 1. |
|
|
| 2. |
- Lango Allen, Hana, et al.
(författare)
-
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
-
Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
|
|
| 3. |
- Tham, Emma, et al.
(författare)
-
A novel phenotype in N-glycosylation disorders: Gillessen-Kaesbach-Nishimura skeletal dysplasia due to pathogenic variants in ALG9.
- 2015
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813.
-
Tidskriftsartikel (refereegranskat)abstract
- A rare lethal autosomal recessive syndrome with skeletal dysplasia, polycystic kidneys and multiple malformations was first described by Gillessen-Kaesbach et al and subsequently by Nishimura et al. The skeletal features uniformly comprise a round pelvis, mesomelic shortening of the upper limbs and defective ossification of the cervical spine. We studied two unrelated families including three affected fetuses with Gillessen-Kaesbach-Nishimura syndrome using whole-exome and Sanger sequencing, comparative genome hybridization and homozygosity mapping. All affected patients were shown to have a novel homozygous splice variant NM_024740.2: c.1173+2T>A in the ALG9 gene, encoding alpha-1,2-mannosyltransferase, involved in the formation of the lipid-linked oligosaccharide precursor of N-glycosylation. RNA analysis demonstrated skipping of exon 10, leading to shorter RNA. Mass spectrometric analysis showed an increase in monoglycosylated transferrin as compared with control tissues, confirming that this is a congenital disorder of glycosylation (CDG). Only three liveborn children with ALG9-CDG have been previously reported, all with missense variants. All three suffered from intellectual disability, muscular hypotonia, microcephaly and renal cysts, but none had skeletal dysplasia. Our study shows that some pathogenic variants in ALG9 can present as a lethal skeletal dysplasia with visceral malformations as the most severe phenotype. The skeletal features overlap with that previously reported for ALG3- and ALG12-CDG, suggesting that this subset of glycosylation disorders constitutes a new diagnostic group of skeletal dysplasias.European Journal of Human Genetics advance online publication, 13 May 2015; doi:10.1038/ejhg.2015.91.
|
|
| 4. |
- Yu, Meng, et al.
(författare)
-
Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19
- 2023
-
Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease. T follicular helper cells (Tfh) enhance antibody responses and can circulate or be resident in lymph nodes. Here the authors show that during acute SARS-CoV-2 infection, circulating Tfh cells correlate with antibody titres and plasmablast levels but in more severe COVID-19 cases, cTfh generation is delayed.
|
|
| 5. |
- Akselsson, Anna
(författare)
-
Awareness of fetal movements and pregnancy outcomes
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fetal movements are one, among others, of the measurable factors indicating wellbeing of the fetus. Decreased fetal movements are associated with intrauterine growth restriction and stillbirth. Women with experience of stillbirth have often noticed decreased and weaker fetal movements preceding the intrauterine death. Further, seeking care for decreased fetal movements is a common reason for unscheduled contact with health care. The aim of this thesis was to investigate whether a method, aimed to increase women’s awareness of the fetal movement pattern, had an effect on pregnancy outcomes. Further, the thesis aimed to study pregnancy outcomes for women seeking care for decreased or altered fetal movements.In Study I, 2683 women completed questionnaires when they presented for decreased fetal movements, after an examination of their unborn baby, that did not result in any interventions aimed at ending the pregnancy. In Studies II–IV, we evaluated Mindfetalness, a method aimed to increase women’s awareness of the fetal movement pattern. Women were given a leaflet of how to practise Mindfetalness in third trimester: lie down on your side when the baby is awake and focus on the strength, character and frequency of the movements for about 15 minutes daily (but do not count each movement). Women’s attitudes to and compliance with Mindfetalness were investigated in Study II, comprising 104 women. In studies III-IV we studied the effect of Mindfetalness on pregnancy outcomes and, through cluster-randomisation, 19 639 women in Stockholm were randomised to Mindfetalness and 20 226 to routine care. Study IV comprised a sub-analysis, where we compared women born in Somalia and Sweden.Women in the Mindfetalness group (Study III) had spontaneous onset of labour to a higher extent (RR 1.02, CI 1.01–1.03), less cesarean sections (RR 0.95, CI 0.91–0.99) and labour inductions (RR 0.96, CI 0.92–1.00), than women in the Routine-care group. More women in the Mindfetalness group contacted healthcare due to decreased fetal movements (RR 1.72, CI 1.57–1.87). A decreased number of babies born small for gestational age (RR 0.95, CI 0.90–1.00) and those transferred to neonatal care (RR 0.93, CI 0.86–1.00) was seen in the Mindfetalness group. No differences were found in Apgar score <7 at 5 minutes. Women born in Somalia had a higher risk of Apgar score <7 at 5 minutes (RR 2.17, CI 1.19–3.61) and of having a baby small for gestational age (RR 2.19, CI 1.85–2.56), than women born in Sweden (Study IV). The majority of the women had a positive attitude towards Mindfetalness and practised the method daily (Study II). Women contacting healthcare due to decreased fetal movements had labour induction to a higher extent than women not seeking care due to decreased fetal movements (Study I).Increased maternal awareness of fetal movements by Mindfetalness in the third trimester is advantageous for mother and baby. Spontaneous start of labour increased and interventions, notably cesarean sections, decreased. Fewer babies were born small for gestational age and in need of neonatal care. Women expressed having positive attitudes to the method and feelings of safety and calm, when they practised Mindfetalness.
|
|
| 6. |
- Andréasson, Sven, et al.
(författare)
-
Behandling av alkohol- och narkotikaproblem : En evidensbaserad kunskapssammanställning
- 2001
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Utvärderingens syfteMissbruk och beroende av alkohol är ett av de största folkhälsoproblemen. Narkotikamissbruk är mindre vanligt men har stora medicinska konsekvenser för de berörda. De sociala och juridiska aspekterna är betydande. En kritisk genomgång av litteraturen vad avser behandling av abstinens, protraherad abstinens, behandling i syfte att förhindra återfall, psykologiska och sociala behandlingar för att minska återfallsrisken, behandlingsprogram och institutionsvårdens roll, samt behandling av missbruk under graviditet. Dessutom en granskning av mini-intervention i primärvård och annan vård vars syfte är att minska konsumtionen hos högkonsumenter av alkohol. Nyligen gjorda meta-analyser inom området värderas och särskild vikt fästs vid interventioner som finns eller lätt kan introduceras i den svenska vårdorganisationen. Behandlingsprogram för patienter med samtidig annan psykisk störning värderas.Så kallat lågdosberoende av bensodiazepiner och andra lugnande medel eller sömnmedel behandlas inte. Inte heller belyses effekten av behandlingar vars primära mål är kroppsliga komplikationer av missbruket, och inte heller granskas metoder att minska tillgänglighet.TillvägagångssättStrukturerad översikt, kostnadsanalyser.Insamling av primärdataSystematisk sökning i relevanta databaser, litteraturlistor i påträffade studier samt i aktuella monografier. Ingen bakre tidsbegränsning och sökning i databaser till och med februari 1999.Utgångspunkt för urval av dataHuvudsakligen randomiserade, kontrollerade, dubbelblinda studier, samt metaanalyser som baseras på sådana studier. Vad gäller långtidsförlopp och ekonomiska analyser även kohortstudier och andra naturalistiska studier.Genomgång av publikationenSamtliga studier värderas med hjälp av en i gruppen utarbetad, och med övriga psykiatriprojekt gemensam, kvalitetsmall. Alla centrala studier läses av minst två i gruppen.Färdiga manuskript värderas av styrelse, expertgrupp samt externa granskare.
|
|
| 7. |
|
|
| 8. |
- Andrén, Anna, et al.
(författare)
-
Miscommunication influences how women act when fetal movements decrease : An interview study with Swedish Somali migrant women
- 2023
-
Ingår i: Midwifery. - 0266-6138 .- 1532-3099. ; 126
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To explore how Swedish Somali migrant women perceive fetal movements, process information about fetal movements, and take actions if decreased fetal activity occurs.DESIGN: A qualitative study based on individual semi-structured interviews. The interviews were analysed using content analysis.SETTING: The study was conducted in Sweden.PARTICIPANTS: Swedish Somali migrant women (n=15) pregnant in their third trimester or recently given birth.FINDINGS: The analysis led to the main category: tailored information about fetal movements enhances the possibility to seek care if the movements decrease. The results are described in the generic categories: explanatory models determine action; and understand and interpret information.KEY CONCLUSIONS: Miscommunication on fetal movements can be a hurdle for Swedish Somali migrant women that may have impact on stillbirth prevention and the quality of care. Improved communication and information tailored to individual needs is essential to achieve equality for women and their newborns.IMPLICATIONS FOR PRACTICE: The midwife can be used as a hub for reassuring that adequate information about fetal movements reaches each individual woman in antenatal care. Individualised information on fetal movements based on the women's own understanding is suggested to increase the possibility that the pregnant woman will seek care if the movements decrease. Somali women's verbal communication can be used to spread accurate information in the Somali community on the importance of seeking care if fetal movements decrease.
|
|
| 9. |
- Andrén, Anna, et al.
(författare)
-
One size does not fit all : Perspectives from Swedish midwives on fetal movement counselling
- 2024
-
Ingår i: Women and Birth. - 1871-5192 .- 1878-1799. ; 37:4
-
Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: Migration continues to play a role in determining health outcomes related to pregnancy and childbirth in Sweden.BACKGROUND: Migrant women have, compared to Swedish-born women, increased risks of adverse birth outcomes. Previous research suggests that migrant women seek care for decreased fetal movements less than Swedish-born women. Given these documented risks, understanding midwives' perspectives in this context is crucial to address maternal health inequities.AIM: To explore midwives' experiences conveying information about fetal movement to migrant women in antenatal healthcare settings.METHODS: Semi-structured, individual interviews with midwives (n=15) experienced in providing information about fetal movements to migrant women. The interviews were analysed using reflexive thematic analysis.FINDINGS: The midwives' efforts to compensate for the deficiencies within the antenatal healthcare organisation and to ensure that all women received access to information and care regarding fetal movements are described in four themes: (a) building a trusting relationship; (b) empowering women through guidance and support; (c) overcoming communication challenges; and d) navigating safety measures.DISCUSSION: Our findings suggest that the standard antenatal care programme does not support midwives to provide holistic and individualised care that aligns with midwifery care philosophy.CONCLUSION: To reduce health inequities for migrant women, this study highlights the need for more flexible guidelines within the standard antenatal care programme. These guidelines should prioritise the individual woman's needs over institutional protocols, acknowledge the midwife-woman relationship as the core of midwifery practice and support midwives to build a partnership with women through continuity of care.
|
|
| 10. |
|
|
