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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Shi, Tian-Le, et al.
(författare)
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High-quality genome assembly enables prediction of allele-specific gene expression in hybrid poplar
- 2024
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Ingår i: Plant Physiology. - : Oxford University Press. - 0032-0889 .- 1532-2548. ; 195:1, s. 652-670
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Tidskriftsartikel (refereegranskat)abstract
- Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid “84K” (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.
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| 4. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 5. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 6. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 7. |
- Zhao, Xue-Ke, et al.
(författare)
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Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.
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| 8. |
- Ariyawansa, Hiran A., et al.
(författare)
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Fungal diversity notes 111–252—taxonomic and phylogenetic contributions to fungal taxa
- 2015
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 75, s. 27-274
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Tidskriftsartikel (refereegranskat)abstract
- This paper is a compilation of notes on 142 fungal taxa, including five new families, 20 new genera, and 100 new species, representing a wide taxonomic and geographic range. The new families, Ascocylindricaceae, Caryosporaceae and Wicklowiaceae (Ascomycota) are introduced based on their distinct lineages and unique morphology. The new Dothideomycete genera Pseudomassariosphaeria (Amniculicolaceae), Heracleicola, Neodidymella and P s e u d o m i c ros p h a e r i o p s i s ( D id y m e l l a c e a e ) , P s e u d o p i t h o m y c e s ( D i d y m o s p h a e r i a c e a e ) , Brunneoclavispora, Neolophiostoma and Sulcosporium (Halotthiaceae), Lophiohelichrysum (Lophiostomataceae), G a l l i i c o l a , Popul o c re s c e n t i a a nd Va g i c o l a (Phaeosphaeriaceae), Ascocylindrica (Ascocylindricaceae), E l o n g a t o p e d i c e l l a t a ( R o u s s o e l l a c e a e ) , Pseudoasteromassaria (Latoruaceae) and Pseudomonodictys (Macrodiplodiopsidaceae) are introduced. The newly described species of Dothideomycetes (Ascomycota) are Pseudomassariosphaeria bromicola (Amniculicolaceae), Flammeascoma lignicola (Anteagloniaceae), Ascocylindrica marina (Ascocylindricaceae) , Lembosia xyliae (Asterinaceae), Diplodia crataegicola and Diplodia galiicola ( B o t r yosphae r i a cea e ) , Caryospor a aquat i c a (Caryosporaceae), Heracleicola premilcurensis and Neodi dymell a thai landi cum (Didymellaceae) , Pseudopithomyces palmicola (Didymosphaeriaceae), Floricola viticola (Floricolaceae), Brunneoclavispora bambusae, Neolophiostoma pigmentatum and Sulcosporium thailandica (Halotthiaceae), Pseudoasteromassaria fagi (Latoruaceae), Keissleriella dactylidicola (Lentitheciaceae), Lophiohelichrysum helichrysi (Lophiostomataceae), Aquasubmersa japonica (Lophiotremataceae) , Pseudomonodictys tectonae (Macrodiplodiopsidaceae), Microthyrium buxicola and Tumidispora shoreae (Microthyriaceae), Alloleptosphaeria clematidis, Allophaeosphaer i a c y t i s i , Allophaeosphae r i a subcylindrospora, Dematiopleospora luzulae, Entodesmium artemisiae, Galiicola pseudophaeosphaeria, Loratospora(Basidiomycota) are introduced together with a new genus Neoantrodiella (Neoantrodiellaceae), here based on both morphology coupled with molecular data. In the class Agaricomycetes, Agaricus pseudolangei, Agaricus haematinus, Agaricus atrodiscus and Agaricus exilissimus (Agaricaceae) , Amanita m e l l e i a l b a , Amanita pseudosychnopyramis and Amanita subparvipantherina (Amanitaceae), Entoloma calabrum, Cora barbulata, Dictyonema gomezianum and Inocybe granulosa (Inocybaceae), Xerocomellus sarnarii (Boletaceae), Cantharellus eucalyptorum, Cantharellus nigrescens, Cantharellus tricolor and Cantharellus variabilicolor (Cantharellaceae), Cortinarius alboamarescens, Cortinarius brunneoalbus, Cortinarius ochroamarus, Cortinarius putorius and Cortinarius seidlii (Cortinariaceae), Hymenochaete micropora and Hymenochaete subporioides (Hymenochaetaceae), Xylodon ramicida (Schizoporaceae), Colospora andalasii (Polyporaceae), Russula guangxiensis and Russula hakkae (Russulaceae), Tremella dirinariae, Tremella graphidis and Tremella pyrenulae (Tremellaceae) are introduced. Four new combinations Neoantrodiella gypsea, Neoantrodiella thujae (Neoantrodiellaceae), Punctulariopsis cremeoalbida, Punctulariopsis efibulata (Punctulariaceae) are also introduced here for the division Basidiomycota. Furthermore Absidia caatinguensis, Absidia koreana and Gongronella koreana (Cunninghamellaceae), Mortierella pisiformis and Mortierella formosana (Mortierellaceae) are newly introduced in the Zygomycota, while Neocallimastix cameroonii and Piromyces irregularis (Neocallimastigaceae) ar e i n t roduced i n the Neocallimastigomycota. Reference specimens or changes in classification and notes are provided for Alternaria ethzedia, Cucurbitaria ephedricola, Austropleospora, Austropleospora archidendri, Byssosphaeria rhodomphala, Lophiostoma caulium, Pseudopithomyces maydicus, Massariosphaeria, Neomassariosphaeria and Pestalotiopsis montellica.
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| 9. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 10. |
- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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