| 1. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 2. |
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| 3. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 4. |
- Björner, Sofie, et al.
(författare)
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Downregulation of miR-92a Is Associated with Aggressive Breast Cancer Features and Increased Tumour Macrophage Infiltration.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: MicroRNAs are small non-coding RNAs involved in the regulation of gene expression on a posttranscriptional level. These regulatory RNAs have been implicated in numerous cellular processes and are further deregulated in different cancer types, including breast cancer. MiR-92a is part of the miR-17∼92 cluster, which was first reported to be linked to tumourigenesis. However, little is known about the expression of miR-92a in breast cancer and potential associations to tumour properties. The expression of miR-92a was therefore characterized in 144 invasive breast cancer samples using in situ hybridization and related to clinico-pathological data as well as to selected key properties of the tumour stroma, including the presence of macrophages (CD68) and cancer activated fibroblasts (alpha-SMA). METHODOLOGY/PRINCIPAL FINDINGS: To measure miR-92a levels, an in situ hybridisation protocol was developed and validated using cell lines and miR-92a inhibitors. The expression in the tumour samples was objectively evaluated using digital image analysis program subtracting background activities. We found that the miR-92a expression varied between tumours and was inversely correlated to tumour grade (r = -0.276, p = 0.003) and recurrence-free survival (p = 0.008) and provided independent prognostic information in multivariate Cox analysis (HR: 0.375, CI: 0.145-0.972, p = 0.043). MiR-92a was moreover inversely correlated to the number of infiltrating macrophages in the tumour stroma (r = -0.357, p<0.001), and downregulation of miR-92a promoted cell migration (p<0.01). CONCLUSIONS/SIGNIFICANCE: This study demonstrates that downregulation of miR-92a in breast cancer is linked to key epithelial and stromal properties as well as clinical outcome.
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| 5. |
- Brout, Dillon, et al.
(författare)
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The Pantheon+ analysis : cosmological constraints
- 2022
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 938:2
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Tidskriftsartikel (refereegranskat)abstract
- We present constraints on cosmological parameters from the Pantheon+ analysis of 1701 light curves of 1550 distinct Type Ia supernovae (SNe Ia) ranging in redshift from z = 0.001 to 2.26. This work features an increased sample size from the addition of multiple cross-calibrated photometric systems of SNe covering an increased redshift span, and improved treatments of systematic uncertainties in comparison to the original Pantheon analysis, which together result in a factor of 2 improvement in cosmological constraining power. For a flat ΛCDM model, we find ΩM = 0.334 ± 0.018 from SNe Ia alone. For a flat w0CDM model, we measure w0 = −0.90 ± 0.14 from SNe Ia alone, H0 = 73.5 ± 1.1 km s−1 Mpc−1 when including the Cepheid host distances and covariance (SH0ES), and w0 = -0.978-+0.0310.024 when combining the SN likelihood with Planck constraints from the cosmic microwave background (CMB) and baryon acoustic oscillations (BAO); both w0 values are consistent with a cosmological constant. We also present the most precise measurements to date on the evolution of dark energy in a flat w0waCDM universe, and measure wa = -0.1-+2.00.9 from Pantheon+ SNe Ia alone, H0 = 73.3 ± 1.1 km s−1 Mpc−1 when including SH0ES Cepheid distances, and wa = -0.65-+0.320.28 when combining Pantheon+ SNe Ia with CMB and BAO data. Finally, we find that systematic uncertainties in the use of SNe Ia along the distance ladder comprise less than one-third of the total uncertainty in the measurement of H0 and cannot explain the present “Hubble tension” between local measurements and early universe predictions from the cosmological model.
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| 6. |
- Edman, Mattias, et al.
(författare)
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Effects of enhanced tree growth rate on the decay capacities of three saprotrophic wood-fungi
- 2006
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 232:1-3, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- The structure of Scandinavian boreal forests has changed in many ways as a result of modern intensive forestry. One of the most fundamental changes is the loss of coarse woody debris (CWD), which has adversely affected many wood-inhabiting species. The consequences of reductions in CWD and its variability have received much attention in the literature recently. However, a neglected substratum change with possible profound ecological implications is enhanced tree growth rate due to forestry practices such as thinning and fertilization. In the study presented here we investigated how tree growth rate influenced the decay capacity of two threatened species, Phlebia centrifuga and Fomitopsis rosea, and a common species, F. pinicola, of saprotrophic wood-decay fungi. Their decay capacity was measured as the weight loss they caused in Picea abies wood-discs categorised as fast-, moderately-, and slow-grown. The results show that the rates of decay caused by all three species were highest in fast-grown wood cut in thinnings, and lowest in slow-grown wood cut in extensively managed stands. None of the stands had been fertilised. Interestingly, rate of decay caused by the common generalist fungus F. pinicola was 50% higher in fast-grown wood than in slow-grown wood, suggesting that the turnover of dead wood is much higher in intensively managed forests. Thus, the time window for wood-living species to colonize CWD, which is a transient habitat even in old-growth forests, is even shorter in intensively managed forests. This may adversely affect species with poor dispersal ability. Moreover, F. rosea decayed the slow-grown wood significantly more rapidly than the other species. This suggests that it may be adapted to such substrates, and that F. rosea may be favoured in old-growth forests where trees generally have slower growth rates than in managed forest. For P. centrifuga, there was a large variation in its decay capacity among genets, indicating a need for further studies on the genetics of threatened wood-fungi, given the species’ fragmented distribution.
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| 7. |
- Feinberg, Alexandra J., et al.
(författare)
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X-ray diffractive imaging of highly ionized helium nanodroplets
- 2022
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Ingår i: Physical Review Research. - 2643-1564. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Finding the lowest energy configuration of N unit charges on a sphere, known as Thomson's problem, is a long-standing query which has only been studied via numerical simulations. We present its physical realization using multiply charged He nanodroplets. The charge positions are determined by x-ray coherent diffractive imaging with Xe as a contrast agent. In neutral droplets, filaments resulting from Xe atoms condensing on quantum vortices are observed. Unique to charged droplets, however, Xe clusters that condense on charges are distributed on the surface in lattice-like structures, introducing He droplets as experimental model systems for the study of Thomson's problem.
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| 8. |
- Felix, Janine F, et al.
(författare)
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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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| 9. |
- Hederstierna, Christina, et al.
(författare)
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The prevalence of Connexin 26 mutations in the Swedish population
- 2005
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Ingår i: Audiological Medicine. - : Informa Healthcare. - 1651-386X .- 1651-3835. ; 3:3, s. 154-158
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in GJB2, the gene encoding the protein Connexin 26, have been shown to account for as much as 50% of autosomal recessive, non-syndromic childhood hearing loss (ARNSHL). Early, correct diagnosis and intervention have greatly improved the possibilities for these children in learning and developing language skills. In recent years, many reports from varied parts of the world have described the local scene of mutations in Connexin 26. The prevalence differs with geographic location and assessment procedures. Mutations in Connexin 26 have until recently been identified in very few cases in Sweden, Norway and Denmark, and nationwide population samples have not been studied in the Scandinavian countries. In this study we present the results of a large nationwide and a regional study of the prevalence of the 35delG, L90P and 167delT mutations of the GJB2 gene in Sweden. A total of 2052 samples (dried blood spots) were analysed. 1501 samples were collected representing all of Sweden and 551 samples from northern Sweden. The allele frequencies in Sweden were found to be 35delG, 0.83%; L90P, 0.30%; and 167delT, 0%. The prevalence of mutations in Connexin 26 in Sweden seems to be comparable to that in other northern European countries.
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| 10. |
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| 11. |
- Löw, Karin, et al.
(författare)
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Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses
- 2023
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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 95:11
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Tidskriftsartikel (refereegranskat)abstract
- The emerging viruses SARS-CoV-2 and arenaviruses cause severe respiratory and hemorrhagic diseases, respectively. The production of infectious particles of both viruses and virus spread in tissues requires cleavage of surface glycoproteins (GPs) by host proprotein convertases (PCs). SARS-CoV-2 and arenaviruses rely on GP cleavage by PCs furin and subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P), respectively. We report improved luciferase-based reporter cell lines, named luminescent inducible proprotein convertase reporter cells that we employ to monitor PC activity in its authentic subcellular compartment. Using these sensor lines we screened a small compound library in high-throughput manner. We identified 23 FDA-approved small molecules, among them monensin which displayed broad activity against furin and SKI-1/S1P. Monensin inhibited arenaviruses and SARS-CoV-2 in a dose-dependent manner. We observed a strong reduction in infectious particle release upon monensin treatment with little effect on released genome copies. This was reflected by inhibition of SARS-CoV-2 spike processing suggesting the release of immature particles. In a proof of concept experiment using human precision cut lung slices, monensin potently inhibited SARS-CoV-2 infection, evidenced by reduced infectious particle release. We propose that our PC sensor pipeline is a suitable tool to identify broad-spectrum antivirals with therapeutic potential to combat current and future emerging viruses.
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| 12. |
- Möller, Daniel, et al.
(författare)
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För ett bättre Lunds universitet nu
- 2015
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Ingår i: LUM: Lunds Universitets Magasin. - : Lund University. - 1653-2295. ; :7, s. 34-34
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Kollektivt författad skrivelse, "För ett bättre Lunds universitet nu", om villkoren för unga forskare vid LU, publicerad i LUM nr 7/2015, s. 34 under rubriken "Ta vara på unga forskares kapacitet!".
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| 13. |
- Møller, Peter, et al.
(författare)
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Inflammation, oxidative stress and genotoxicity responses to biodiesel emissions in cultured mammalian cells and animals
- 2020
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Ingår i: Critical Reviews in Toxicology. - : Informa UK Limited. - 1040-8444 .- 1547-6898. ; 50:5, s. 383-401
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Forskningsöversikt (refereegranskat)abstract
- Biodiesel fuels are alternatives to petrodiesel, especially in the transport sector where they have lower carbon footprint. Notwithstanding the environmental benefit, biodiesel fuels may have other toxicological properties than petrodiesel. Particulate matter (PM) from petrodiesel causes cancer in the lung as a consequence of delivery of genotoxic polycyclic aromatic hydrocarbons, oxidative stress and inflammation. We have reviewed articles from 2002 to 2019 (50% of the articles since 2015) that have described toxicological effects in terms of genotoxicity, oxidative stress and inflammation of biodiesel exhaust exposure in humans, animals and cell cultures. The studies have assessed first generation biodiesel from different feedstock (e.g. rapeseed and soy), certain second generation fuels (e.g. waste oil), and hydrogenated vegetable oil. It is not possible to rank the potency of toxicological effects of specific biodiesel fuels. However, exposure to biodiesel exhaust causes oxidative stress, inflammation and genotoxicity in cell cultures. Three studies in animals have not indicated genotoxicity in lung tissue. The database on oxidative stress and inflammation in animal studies is larger (13 studies); ten studies have reported increased levels of oxidative stress biomarkers or inflammation, although the effects have been modest in most studies. The cell culture and animal studies have not consistently shown a different potency in effect between biodiesel and petrodiesel exhausts. Both increased and decreased potency have been reported, which might be due to differences in feedstock or combustion conditions. In conclusion, combustion products from biodiesel and petrodiesel fuel may evoke similar toxicological effects on genotoxicity, oxidative stress and inflammation.
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| 14. |
- Möller, Rebecca
(författare)
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Makrofyter i Bergträsket och Valkeajärvi : – inventering och utvärdering av metod
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Som ett led i miljöövervakningen av sötvatten i Norrbottens län har inventering av makrofytergenomförts under sensommaren 2005 i två av länets regionala referenssjöar, Bergträsket ochValkeajärvi. Syftet var i första hand att få en bild av sjöarnas växtsamhällen samt att utvärderainventeringsmetoderna.InventeringsmetoderEn kvalitativ och en kvantitativ inventeringsmetod användes. Den kvalitativa metoden går utpå att beskriva växtsamhället i en hel sjö och upprätta en artlista, en metod som gerinformation om sjöns nuvarande status utan att jämförelser med tidigare inventeringar av sjönär nödvändiga. Resultatet blir än mer värdefullt om man gör en översiktskarta över växtsamhällenai sjön. Metoden visade sig ge en bra koppling till vattenkemiska data som tidigareinsamlats. Genom den kvantitativa metoden mäts arters frekvens och täckning i en lokal, enmetod som inte säger något om sjöns nuvarande status om man inte har tillgång till tidigareinventeringsresultat att jämföra med. Den kvantitativa metoden måste alltså följas upp underflera år. Dessutom är den svårare att utföra och efterarbetet mer tidskrävande i jämförelse medden kvalitativa metoden.BergträsketBergträsket är en ganska artrik sjö. Artsammansättningen indikerar att sjön är naturligt någotsur. Detta bekräftas av långa tidsserier vattenkemiska data från miljöövervakningsprogrammet.Artsammansättningen varierar mycket mellan olika delar av sjön. Bestånd av gulnäckros återfinns på alla platser med tillströmmande vatten och lös finsediment- ellergyttjebotten. Bestånd av vekt braxengräs finns där bottnen är något fastare. Några arter(strandranunkel, en kransalg, plattbladig igelknopp, två olika arter näckmossa, hästsvans,sjöfräken och sylört) bildar bara tydligt definierade bestånd på vardera en plats i sjön. I denlokal som inventerades kvantitativt dominerar vekt braxengräs både med avseende påfrekvens och täckning.ValkeajärviValkeajärvi är en ganska artfattig sjö, vilket är vad man förväntar sig med tanke på dessstorlek och geografiska belägenhet. Det finns ingen antydan till varken eutrofiering ellerförsurning. Artsammansättningen varierar mellan olika delar av sjön, men är inte likaheterogen som i Bergträsket. Vekt braxengräs förekommer över hela sjön ner till cirka 2,5 mdjup, men är inte beståndsbildande på platser med lös dybotten. Gul näckros förekommerendast på dybotten, men bildar tydligt definierat bestånd endast på en plats i sjön. Bestånd avandra arter förekommer på flera ställen i sjön. I den lokal som inventerades kvantitativtdominerar vekt braxengräs både med avseende på frekvens och täckning.
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| 15. |
- Passos, Vania, et al.
(författare)
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Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons
- 2024
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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies.
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| 16. |
- Scholten, Rebecca Harnung, et al.
(författare)
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Inhalation of hydrogenated vegetable oil combustion exhaust and genotoxicity responses in humans
- 2021
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 95:10, s. 3407-3416
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Tidskriftsartikel (refereegranskat)abstract
- Biofuels from vegetable oils or animal fats are considered to be more sustainable than petroleum-derived diesel fuel. In this study, we have assessed the effect of hydrogenated vegetable oil (HVO) exhaust on levels of DNA damage in peripheral blood mononuclear cells (PBMCs) as primary outcome, and oxidative stress and inflammation as mediators of genotoxicity. In a randomized cross-over study, healthy humans were exposed to filtered air, inorganic salt particles, exhausts from combustion of HVO in engines with aftertreatment [i.e. emission with nitrogen oxides and low amounts of particulate matter less than 2.5 µm (approximately 1 µg/m3)], or without aftertreatment (i.e. emission with nitrogen oxides and 93 ± 13 µg/m3 of PM2.5). The subjects were exposed for 3 h and blood samples were collected before, within 1 h after the exposure and 24 h after. None of the exposures caused generation of DNA strand breaks and oxidatively damaged DNA, or affected gene expression of factors related to DNA repair (Ogg1), antioxidant defense (Hmox1) or pro-inflammatory cytokines (Ccl2, Il8 and Tnfa) in PBMCs. The results from this study indicate that short-term HVO exhaust exposure is not associated with genotoxic hazard in humans.
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| 17. |
- Thornton, Nicole, et al.
(författare)
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Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44.
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| 18. |
- Tyrrell, Jessica, et al.
(författare)
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Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.
- 2016
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 315:11, s. 1129-40
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Tidskriftsartikel (refereegranskat)abstract
- Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.Offspring birth weight from 18 studies.Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P=.008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P=7×10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P=1×10(-5)), respectively. A 1-SD (≈4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD (≈7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD (≈10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
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| 19. |
- Vergmann, Anna Stage, et al.
(författare)
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Heritability of retinal vascular fractals : A twin study
- 2017
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 58:10, s. 3997-4002
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. METHODS. This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50º, disc-centered fundus photographs, the retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficients. Falconer’s formula and quantitative genetic models were used to determine the genetic component of variation. RESULTS. The mean fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0.0002) in monozygotic twins than in dizygotic twins (0.108, P = 0.46), corresponding to a heritability h2 for the fractal dimension of 0.79. In quantitative genetic models, dominant genetic effects explained 54% of the variation and 46% was individually environmentally determined. CONCLUSIONS. In young adult twins, the branching pattern of the retinal vessels demonstrated a higher structural similarity in monozygotic than in dizygotic twin pairs. The retinal vascular fractal dimension was mainly determined by genetic factors, which accounted for 54% of the variation. The genetically predetermination of the retinal vasculature may affect the retinal response to potential vascular disease in later life.
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| 20. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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