Prcmd-G-1
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010001212 | EGA |
REPOSITORIES: EGA
Publications
Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.
McGinnis Ralph R Steinthorsdottir Valgerdur V Williams Nicholas O NO Thorleifsson Gudmar G Shooter Scott S Hjartardottir Sigrun S Bumpstead Suzannah S Stefansdottir Lilja L Hildyard Lucy L Sigurdsson Jon K JK Kemp John P JP Silva Gabriela B GB Thomsen Liv Cecilie V LCV Jääskeläinen Tiina T Kajantie Eero E Chappell Sally S Kalsheker Noor N Moffett Ashley A Hiby Susan S Lee Wai Kwong WK Padmanabhan Sandosh S Simpson Nigel A B NAB Dolby Vivien A VA Staines-Urias Eleonora E Engel Stephanie M SM Haugan Anita A Trogstad Lill L Svyatova Gulnara G Zakhidova Nodira N Najmutdinova Dilbar D Dominiczak Anna F AF Gjessing Håkon K HK Casas Juan P JP Dudbridge Frank F Walker James J JJ Pipkin Fiona Broughton FB Thorsteinsdottir Unnur U Geirsson Reynir T RT Lawlor Debbie A DA Iversen Ann-Charlotte AC Magnus Per P Laivuori Hannele H Stefansson Kari K Morgan Linda L
Nature genetics 20170619 8
Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility loc ...[more]
Similar Datasets
Project description:Background: Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. The placenta is central to the etiology of PE. However, how and to what extent the placenta contributes to worse PE outcomes in persons of African ancestry is yet to be fully elucidated. Objective: We aimed to identify molecular pathways that are unique or enriched in placentas of parturient persons of African ancestry with PE with severe features (sPE) compared to those of Asian and European ancestry with sPE. Study design: Bulk RNA sequencing was performed on 50 placentas from parturient persons with sPE of African (n=9), Asian (n=18) and European (n=23) ancestries and 73 normotensive controls of African (n=9), Asian (n=15) and European (n=49) ancestries. Results: Metabolism, hormone regulation and hypoxia/angiogenesis genes, previously described to be upregulated in PE, including: LEP, PAPPA2, INHA, FSTL3, FLT1, PHYHIP and ENG, were upregulated in sPE across ancestries, with high expression of FSTL3 being additionally associated with intrauterine growth restriction (p<.0001). Notably, LEP, FLT1 and PHYHIP were more highly upregulated in sPE placentas from parturient persons of African versus Asian ancestry. Genes associated with allograft rejection and adaptive immune response were selectively upregulated in placentas from African ancestry parturitions and not in those of Asian and European ancestries. Among the allograft rejection/adaptive immune response genes, IL3RA was of particular interest because the patient with the highest placental IL3RA level, a woman of African ancestry with IL3RA levels 4.5-fold above the average for African ancestry parturitions with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients of Asian and European ancestries with the highest IL3RA levels for their ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p=.0005). Conclusions: African ancestry parturitions are associated with higher placental upregulation of metabolism (LEP) and hypoxia/angiogenesis (FLT1) genes, and selective upregulation of allograft rejection/adaptive immune response genes, including IL3RA. High placental expression of IL3RA may predict worse maternal cardiovascular outcomes, including peripartum cardiomyopathy. Studies evaluating placental IL3RA levels in peripartum cardiomyopathy cohorts are therefore warranted, as are broader studies evaluating placental factors in maternal cardiovascular outcomes postpartum.
2023-11-09 | GSE234729 | GEO
Project description:Spotted hyena (Crocuta crocuta) is the only extant species of the genus Crocuta, which once occupied a much wider range during the Pliocene and Pleistocene. However, its origin and evolutionary history is somewhat contentious due to discordances being found between morphological, nuclear, and mitochondrial data. Due to the limited molecular data from east Asian Crocuta, and the difficulty of extracting ancient DNA from this area, here we present proteomic analysis of cave hyenas from three locations in northern China. This marks the first proteomic data generated from cave hyenas, adding new molecular data to the east Asian populations. Phylogenetic analysis based on these protein sequences reveals two different groups of cave hyenas in east Asia, one of which could not be distinguished from modern spotted hyenas from northern Africa, tentatively the result of previously suggested gene flow between these lineages. With developments of instrumentation and analytical methods, proteomics holds promising potential for the phylogenetic reconstruction of ancient fauna previously thought to be unreachable using ancient DNA.
2020-10-19 | PXD020530 | Pride
Project description:Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with molecular disease pathogenesis. Nonsynonymous single nucleotide polymorphisms (SNPs) encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis shows that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2=0.9905). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma (ULM) tissues combined resulted in the quantitation of 62 pAIMs that correlate with self-described race and genotype-confirmed patient ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. These efforts describe a generalized set of markers for proteoancestry assessment that will further support studies investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.
2022-02-16 | PXD029323 | Pride
Project description:Genetic analyses for bipolar disorder (BPD) have achieved prominent success in Europeans in recent years, whereas its genetic basis in other populations remains relatively less understood. We herein report that the lead risk locus for BPD in European genome-wide association studies (GWAS), the single nucleotide polymorphism (SNP) rs9834970 near TRANK1 at 3p22 region, is also genome-wide significantly associated with BPD in 5,748 cases and 65,361 controls of East Asian origin. In this study, we performed RAN-seq analysis of cultured rat neurons treated with shRNA knockdown of Trank1.
2020-07-02 | GSE153638 | GEO
Project description:GBS sequencing of canola from Northern European populations
| PRJNA835738 | ENA
Project description:21 unlinked autosomal microsatellite loci for 30 Central Asian populations
| EGAD00010000536 | EGA
Project description:We performed a comparative study of European and Asian populations using Illumina HM450K. We found that the majority of Infinium probes, which differentiated two examined groups, had SNPs in their target sequence. We investigated the impact of those SNPs on methylation readouts by Illumina HM450K Array. Our study clearly demonstrates that SNP variation existing in the genome, if not accounted for, may lead to false interpretation of the methylation signal differences suggested by some of the Illumina Infinium probes.
2015-12-03 | GSE73901 | GEO
Project description:Southern California (USA) populations of the intertidal marine snail Chlorostoma (formerly Tegula) funebralis are generally exposed to higher air and water temperatures than northern California populations. Previous studies have shown that southern populations are more tolerant of heat stress than northern populations. To assess the potential role of gene regulation in these regional differences, we examined transcriptome responses to thermal stress in two southern and two northern populations of C. funebralis. Snails from the four populations were acclimated to a common lab environment, exposed to a heat stress representative of natural low tide conditions, and then analyzed using RNA-Seq to characterize changes in gene expression associated with stress and differences in expression across geographic regions. Changes in expression following stress were dominated by genes involved in apoptosis, the inflammatory response, response to mis and unfolded proteins, and ubiquitination of proteins. Heat shock proteins (Hsps) were up-regulated in both northern and southern populations. However, while the magnitude of the response was significantly greater in northern populations for the majority of Hsp70s, the southern populations showed a greater up-regulation for roughly half of the Hsp40s, which are co-chaperones for Hsp70s. Differential expression analysis of the control versus treatment genes in the northern and southern populations respectively revealed that 56 genes, many involved in the inflammation and immune response, responded to heat stress only in the northern populations. Moreover, several of the molecular chaperones and antioxidant genes that were not differentially expressed in the southern populations instead showed higher constitutive expression under control conditions compared to the northern populations. The expression levels of some of these constitutive genes such as superoxide dismutase were also found to positively correlate with survival following heat stress. This suggests that expression of these genes has evolved a degree of “frontloading” that may contribute to the higher thermal tolerance of southern populations.
2014-08-20 | GSE57142 | GEO