A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases

Effects of structural heterogeneity of nanostructured copper on the evolution of the sizes of recrystallized grains during annealing

Recrystallization in copper deformed by dynamic plastic deformation was investigated using electron backscatter diffraction. The recrystallized grains show a broad size distribution. The kinetics of grains of different sizes is observed to be different: In the beginning of recrystallization, the area fraction of small recrystallized grains increases rapidly. At later stages of recrystallization, the area fraction of small recrystallized grains is stable, while the area fractions of medium and large recrystallized grains increase. Correlation between the broad grain size distribution (and its evolution) and the heterogeneous deformed microstructure is discussed. © Published under licence by IOP Publishing Ltd.Conference code: 114064; Cited By :1; Export Date: 18 November 2021; Conference Paper; References: Leffers, T., Ray, R.K., (2009) Prog. Mater. Sci., 54, p. 351; Bhattacharyya, A., Rittel, D., Ravichandra, G., (2005) Scr. Mater., 52, p. 657; Luo, Z.P., Mishin, O.V., Zhang, Y.B., Zhang, H.W., Lu, K., (2012) Scr. Mater., 66, p. 355; Hong, C.S., Tao, N.R., Lu, K., Huang, X., (2009) Scr. Mater., 61, p. 289; Morri, K., Meching, H., Nakayama, Y., (1985) Acta Mater, 33, p. 379; Lin, F.X., Zhang, Y.B., Tao, N.R., Pantleon, W., Juul Jensen, D., (2014) Acta Mater, 72, p. 252; Wu, G.L., Juul Jensen, D., (2008) Mater. Charact., 59, p. 794; Pande, C.S., (2000) Proc. 21st Risø Inter. Symposium on Mater. Sci., p. 491; Lin, F.X., Zhang, Y.B., Pantleon, W., Juul Jensen, D., Submitted; Li, Y.S., Tao, N.R., Lu, K., (2008) Acta Mater, 56, p. 230; Li, Y.S., Zhang, Y., Tao, N.R., Lu, K., (2008) Scr. Mater., 59, p. 475; Yan, F., Zhang, H.W., (2012) J Mater. Sci. Technol., 28, p. 289</p

Nature and evolution of Mesozoic-Cenozoic lithospheric mantle beneath the Cathaysia block, SE China

Mantle-derived garnet and spinel peridotite xenoliths and xenocrysts from the Daoxian basalts (151–131 Ma) and the Anyuan lamprophyres (~44 Ma) provide insights into the nature and evolution of subcontinental lithospheric mantle beneath the Cathaysia block, SE China. The Daoxian area lies astride the translithospheric Ningyuan– Jianghua fault zone in western Cathaysia, whereas the Anyuan area lies east of the fault zone. The peridotite xenoliths from both localities have experienced melt extraction (generally 3–10% fractional or batch melting) and subsequent silicate melt metasomatism. Depleted coarse-textured spinel peridotites from Anyuan and localities in East Cathaysia have relatively magnesian olivine (Mg#≥91) and may be relics of the Proterozoic lithospheric upper mantle, preserved locally at shallow levels away from the translithospheric fault. At Daoxian coarse-textured xenoliths are absent, and some xenoliths have sheared microstructures. The minerals of the Daoxian xenoliths have lower Cr# and Mg# than those from Auyuan. The Daoxian xenoliths also have higher bulk CaO+Al₂O₃ contents and FeO/MgO, suggesting more pronounced metasomatism. The differences between the Daoxian and Anyuan xenolith suites reflect their spatial relationship to the translithospheric Ningyuan–Jianghua fault zone, which played an important role in the Mesozoic replacement of Proterozoic lithospheric mantle. The lithospheric mantle information from these localities is combined with published data from other localities to provide the first comprehensive survey of the evolution of the lithospheric mantle beneath the Cathaysia block. The xenolith suites of West and East Cathaysia are interpreted as sampling mixtures of older and newly accreted lithospheric mantle that replaced the Proterozoic lithosphere through extension, thermal erosion and melt metasomatism.25 page(s

Late Mesozoic-Eocene mantle replacement beneath the eastern North China Craton : evidence from the Paleozoic and Cenozoic peridotite xenoliths

Xenolith-bearing Paleozoic kimberlites and Cenozoic basalts from the eastern part of the North China craton provide unusual insights into intraplate processes and Phanerozoic lithospheric evolution. Paleozoic peridotite xenoliths represent samples of ancient cratonic mantle; P-T estimates show that a thick (~230 km), cold (ca 40 mW/m²) lithosphere existed beneath the craton during mid- Ordovician time. However, xenoliths from Tertiary basalts sample a thin (< 90 km), hot (mean geotherm ca 80 mW/m²), compositionally heterogeneous lithosphere beneath the same area in Cenozoic time. Fertile, spinel-facies mantle makes up much of the Cenozoic lithosphere beneath the eastern North China craton, especially in regions along the translithospheric Tanlu fault. However, refractory spinel-facies xenoliths are found locally along the north-south gravity lineament in areas far away from the Tanlu fault. These refractory xenoliths are interpreted as derived from shallow relics of the cratonic mantle embedded in more fertile Cenozoic lithosphere. The increasing incidence of fine-grained, sheared microstructures in xenoliths from the north-south gravity lineament progressively toward the Tanlu fault suggests that the translithospheric fault system played an important role in the Mesozoic-Cenozoic replacement of pre-existing lithospheric mantle by more fertile material. Modification of cratonic mantle beneath the eastern North China craton involved irregular replacement of old lithosphere by cooling products of weakly depleted asthenosphere welling up along major shear systems. This lithosphere replacement was accompanied by an elevated geotherm and a shallower asthenosphere-lithosphere boundary.16 page(s

3.6 Ga lower crust in central China : new evidence on the assembly of the North China craton

U-Pb and Hf isotope analyses of zircons from felsic granulite xenoliths in Mesozoic volcanics reveal Early Archean (≥3.6 Ga) lower crust beneath the younger (<2.85 Ga) southern margin of the North China craton, and suggest that the eastern part of the craton formed a coherent block by 3.6 Ga. Hf model ages indicate extraction of protoliths from the mantle ca. 4 Ga or earlier, followed by remelting at 3.6–3.7 Ga. Hf isotope data require both recrystallization of magmatic zircons, and growth of new zircon, up to ca. 1.9 Ga. One sample records 2.1–1.9 Ga remelting of a 2.5 Ga protolith. If large parts of the exposed upper continental crust elsewhere also are underlain by older lower crust, estimates of crustal growth rates through time will require revision.4 page(s