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- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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| 2. |
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| 3. |
- Ruwald, Anne Christine H., et al.
(författare)
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Losartan versus atenolol-based antihypertensive treatment reduces cardiovascular events especially well in elderly patients : the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study
- 2012
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 30:6, s. 1252-1259
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study has previously demonstrated a beneficial effect of losartan compared to atenolol-based antihypertensive treatment in patients with essential hypertension and left-ventricular hypertrophy (LVH). However, patient age often influences the choice of antihypertensive drugs. Therefore, we investigated the influence of age on the effects of losartan versus atenolol-based antihypertensive treatment. Methods: A total of 9193 hypertensive patients with LVH aged 45-83 years were followed for a mean of 4.8 years. Blood pressure, high-density lipoprotein cholesterol (HDL-C), Sokolow-Lyon voltage, Cornell voltage-duration product and urine albumin-creatinine ratio (UACR) were measured yearly throughout the study. Patients were divided into two age groups according to the median age of 67 years and the effects of losartan versus atenolol-based antihypertensive treatment on the primary composite endpoint (CEP) consisting of cardiovascular death, nonfatal stroke or nonfatal myocardial infarction were investigated. Results: The beneficial effect of losartan versus atenolol-based treatment was greater in the group of patients older than 67 years [hazard ratio 0.79 (0.69-0.91), P=0.001] compared to the group of patients younger than 67 years [hazard ratio 1.03 (0.82-1.28), P=0809], P=0.045 for interaction. The beneficial effects of losartan versus atenolol-based antihypertensive treatment on pulse pressure, HDL-C, UACR, and Cornell and Sokolow-Lyon voltage were not more pronounced in patients older than 67 years compared to patients younger than 67 years. All five risk factors considered as time-varying covariates predicted CEP independently (P<0.01) with the exception of pulse pressure (P=0.37) and the interaction between age and treatment on outcome remained significant (P=0.042). Conclusions: We showed a greater beneficial effect of losartan versus atenolol-based antihypertensive treatment in the group of patients older than 67 years compared to the group of patients younger than 67 years. This difference was not explained by a more pronounced effect of losartan-based treatment on any of the cardiovascular risk factors demonstrated to have independent prognostic importance.
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| 4. |
- Skotte, Line, et al.
(författare)
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Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:2, s. 555-568
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Tidskriftsartikel (refereegranskat)abstract
- Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10-4). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.
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| 5. |
- Solé Navais, Pol, et al.
(författare)
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Genetic effects on the timing of parturition and links to fetal birth weight.
- 2023
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Ingår i: Nature genetics. - 1546-1718. ; 55:4, s. 559-567
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Tidskriftsartikel (refereegranskat)abstract
- The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n=195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n=136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.
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| 7. |
- Zhang, Wenxin, et al.
(författare)
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Model-data fusion to assess year-round CO2 fluxes for an arctic heath ecosystem in West Greenland (69°N)
- 2019
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 1873-2240 .- 0168-1923. ; 272-273, s. 176-186
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying net CO2 exchange (NEE) of arctic terrestrial ecosystems in response to changes in climatic and environmental conditions is central to understanding ecosystem functioning and assessing potential feedbacks of the carbon cycle to future climate changes. However, annual CO2 budgets for arctic tundra are rare due to the difficulties of performing measurements during non-growing seasons. It is still unclear to what extent arctic tundra ecosystems currently act as a CO2 source, sink or are in balance. This study presents year-round eddy-covariance (EC) measurements of CO2 fluxes for an arctic heath ecosystem on Disko Island, West Greenland (69 °N) over five years. Based on a fusion of year-round EC-derived CO2 fluxes, soil temperature and moisture, the process-oriented model (CoupModel) has been constrained to quantify an annual budget and characterize seasonal patterns of CO2 fluxes. The results show that total photosynthesis corresponds to -202 ± 20 g C m−2 yr-1 with ecosystem respiration of 167 ± 28 g C m-2 yr-1, resulting in NEE of -35 ± 15 g C m-2 yr-1. The respiration loss is mainly described as decomposition of near-surface litter. A year with an anomalously deep snowpack shows a threefold increase in the rate of ecosystem respiration compared to other years. Due to the high CO2 emissions during that winter, the annual budget results in a marked reduction in the CO2 sink. The seasonal patterns of photosynthesis and soil respiration were described using response functions of the forcing atmosphere and soil conditions. Snow depth, topography-related soil moisture, and growing season warmth are identified as important environmental characteristics which most influence seasonal rates of gas exchange.
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