| 11. |
- van der Valk, Ralf J P, et al.
(författare)
-
A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
-
Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
|
|
| 12. |
|
|
| 13. |
- Benzinou, Michael, et al.
(författare)
-
Common nonsynonymous variants in PCSK1 confer risk of obesity.
- 2008
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:8, s. 943-5
-
Tidskriftsartikel (refereegranskat)abstract
- Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.
|
|
| 14. |
- Caporale, N., et al.
(författare)
-
From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
-
Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
|
|
| 15. |
- Felipe, T., et al.
(författare)
-
Three-dimensional structure of a sunspot light bridge
- 2016
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Active regions are the most prominent manifestations of solar magnetic fields; their generation and dissipation are fundamental problems in solar physics. Light bridges are commonly present during sunspot decay, but a comprehensive picture of their role in the removal of the photospheric magnetic field is still lacking. Aims. We study the three-dimensional configuration of a sunspot, and in particular, its light bridge, during one of the last stages of its decay. Methods. We present the magnetic and thermodynamical stratification inferred from full Stokes inversions of the photospheric Si I 10 827 angstrom and Ca I 10 839 angstrom lines obtained with the GREGOR Infrared Spectrograph of the GREGOR telescope at the Observatorio del Teide, Tenerife, Spain. The analysis is complemented by a study of continuum images covering the disk passage of the active region, which are provided by the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory. Results. The sunspot shows a light bridge with penumbral continuum intensity that separates the central umbra from a smaller umbra. We find that in this region the magnetic field lines form a canopy with lower magnetic field strength in the inner part. The photospheric light bridge is dominated by gas pressure (high-beta), as opposed to the surrounding umbra, where the magnetic pressure is higher. A convective flow is observed in the light bridge. This flow is able to bend the magnetic field lines and to produce field reversals. The field lines merge above the light bridge and become as vertical and strong as in the surrounding umbra. We conclude that this occurs because two highly magnetized regions approach each other during the sunspot evolution.
|
|
| 16. |
- Felix, Janine F, et al.
(författare)
-
Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
-
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.
|
|
| 17. |
- Joshi, Jayant, et al.
(författare)
-
Upper chromospheric magnetic field of a sunspot penumbra : observations of fine structure
- 2016
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 596
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. The fine-structure of the magnetic field in a sunspot penumbra in the upper chromosphere is to be explored and compared to that in the photosphere. Methods. Spectropolarimetric observations with high spatial resolution were recorded with the 1.5-m GREGOR telescope using the GREGOR Infrared Spectrograph (GRIS). The observed spectral domain includes the upper chromospheric Hei triplet at 10 830 angstrom and the photospheric Si I 10 827.1 angstrom and Ca I 10 833.4 angstrom spectral lines. The upper chromospheric magnetic field is obtained by inverting the Hei triplet assuming a Milne-Eddington-type model atmosphere. A height-dependent inversion was applied to the Si I 10 827.1 angstrom and Ca I 10 833.4 angstrom lines to obtain the photospheric magnetic field. Results. We find that the inclination of the magnetic field varies in the azimuthal direction in the photosphere and in the upper chromosphere. The chromospheric variations coincide remarkably well with the variations in the inclination of the photospheric field and resemble the well-known spine and interspine structure in the photospheric layers of penumbrae. The typical peak-to-peak variations in the inclination of the magnetic field in the upper chromosphere are found to be 10 degrees-15 degrees, which is roughly half the variation in the photosphere. In contrast, the magnetic field strength of the observed penumbra does not vary on small spatial scales in the upper chromosphere. Conclusions. Thanks to the high spatial resolution of the observations that is possible with the GREGOR telescope at 1.08 microns, we find that the prominent small-scale fluctuations in the magnetic field inclination, which are a salient part of the property of sunspot penumbral photospheres, also persist in the chromosphere, although at somewhat reduced amplitudes. Such a complex magnetic configuration may facilitate penumbral chromospheric dynamic phenomena, such as penumbral micro-jets or transient bright dots.
|
|
| 18. |
- Kiess, W, et al.
(författare)
-
Induction of puberty in the hypogonadal girl--practices and attitudes of pediatric endocrinologists in Europe
- 2002
-
Ingår i: Hormone research. - : S. Karger AG. - 0301-0163. ; 57:1-2, s. 66-71
-
Tidskriftsartikel (refereegranskat)abstract
- The management of children and adolescents with hypogonadism and in particular the induction of puberty in the hypogonadal girl is subject to controversy. Therefore, under the auspices and through organization of the Drugs and Therapeutics Committee of the European Society of Paediatric Endocrinology (ESPE), an interactive voting session and workshop was held at the 39th ESPE Annual Meeting in Brussels to discuss these topics. Common practice in Europe and attitudes of pediatric endocrinologists in Europe were questioned and recorded in the 1.5-hour program. We now report on some of the results of the questionnaires and discussions of that session to further the discussion on and knowledge of current concepts of induction of puberty in the hypogonadal girl in Europe. It became clear from the data accumulated here that the start of treatment, the aims of therapy and the modalities of how to treat the hypogonadal girl vary amongst pediatric endocrinologists in Europe. For example, a chronological age ≧11 years was considered appropriate for the start of estrogen therapy by 40.4% (out of 188 answers), while 47.8 and 7.5% felt that a chronological age ≧13 and ≧15 years respectively was appropriate. In respect to the form and route of estrogen administration, the audience was asked for their common estrogen replacement practice: 31.9% used oral 17β-estradiol treatment, while 10% would prescribe 17β-estradiol transdermal patches. Another 12.2% would recommend conjugated estrogens (e.g. Premarin<sup>®</sup>) orally, 4.8% use oral estradiol valerate and 39.3% ethinylestradiol orally. Only 1.8% out of 229 physicians answering were undecided. In addition, counseling of patients and their families is quite variable and perceptions for example regarding potential pregnancies in affected women are also not uniform. In this report the authors do not want to provide their own personal views but rather reflect current practice in Europe. It is hoped that a more uniform picture will emerge once European and international guidelines on how to treat the girl with hypogonadism will be available and even more discussions amongst doctors from different countries have been led.
|
|
| 19. |
|
|
| 20. |
- Nidens, N., et al.
(författare)
-
Associations of prenatal exposure to phthalates and one phthalate substitute with anthropometric measures in early life : Results from the German LIFE Child cohort study
- 2021
-
Ingår i: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. - : Bailliere Tindall Ltd. - 1521-690X .- 1532-1908. ; 35:5
-
Tidskriftsartikel (refereegranskat)abstract
- Exposure to phthalates is widespread and especially early life stages represent a critical window of exposure. In the present study, we investigated the effect of prenatal exposure to phthalates on birth outcomes and weight development in early life. In 130 mother–child pairs, we estimated the association of concentrations of 13 phthalates in spot-urine samples collected during pregnancy and birth outcomes and weight gain in the first two years of life using robust linear regression. High molecular weight phthalates were inversely associated with birth weight in girls but not in boys. Thus, prenatal exposure to phthalates may affect birth weight in a sex-specific manner.
|
|
