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Dive into the research topics where Yuning Chen is active.

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Featured researches published by Yuning Chen.


Nature Communications | 2013

Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution

Jishi Chen; Quanfei Huang; Dongying Gao; Jun Wang; Yongshan Lang; Tiebang Liu; Bowen Li; Zetao Bai; Luis Goicoechea J; Chengzhi Liang; Caifen Chen; Wenbin Zhang; Silong Sun; Yi Liao; X. Zhang; Lixin Yang; Chi Song; Wang M; Junjie Shi; G.R. Liu; Jinlei Liu; Huanmin Zhou; Wen-Wu Zhou; Qingyi Yu; Na An; Yuning Chen; Qingle Cai; Bingqiang Wang; Boqing Liu; Josine L. Min

The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.


Nature Communications | 2013

A rare functional cardioprotective APOC3 variant has risen in frequency in distinct population isolates.

Ioanna Tachmazidou; George V. Dedoussis; Lorraine Southam; Aliki-Eleni Farmaki; Graham R. S. Ritchie; Dionysia K. Xifara; Angela Matchan; Konstantinos Hatzikotoulas; N W Rayner; Yuning Chen; Toni I. Pollin; O'Connell; Laura M. Yerges-Armstrong; Chrysoula Kiagiadaki; Kalliope Panoutsopoulou; Jeremy Schwartzentruber; Loukas Moutsianas; Emmanouil Tsafantakis; Chris Tyler-Smith; Gilean McVean; Yali Xue; Eleftheria Zeggini

Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies, but the generalizability of such findings remains unknown. Here we genotype 1,267 individuals from a Greek population isolate on the Illumina HumanExome Beadchip, in search of functional coding variants associated with lipids traits. We find genome-wide significant evidence for association between R19X, a functional variant in APOC3, with increased high-density lipoprotein and decreased triglycerides levels. Approximately 3.8% of individuals are heterozygous for this cardioprotective variant, which was previously thought to be private to the Amish founder population. R19X is rare (<0.05% frequency) in outbred European populations. The increased frequency of R19X enables discovery of this lipid traits signal at genome-wide significance in a small sample size. This work exemplifies the value of isolated populations in successfully detecting transferable rare variant associations of high medical relevance.


Molecular Psychiatry | 2018

Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation

Joshua C. Bis; Xueqiu Jian; Brian W. Kunkle; Yuning Chen; Kara L. Hamilton-Nelson; William S. Bush; William Salerno; Daniel Lancour; Yiyi Ma; Alan E. Renton; Edoardo Marcora; John J. Farrell; Yi Zhao; Liming Qu; Shahzad Ahmad; Najaf Amin; Philippe Amouyel; Gary W. Beecham; Jennifer E. Below; Dominique Campion; Camille Charbonnier; Jaeyoon Chung; Paul K. Crane; Carlos Cruchaga; L. Adrienne Cupples; Jean-François Dartigues; Stéphanie Debette; Jean-François Deleuze; Lucinda Fulton; Stacey Gabriel

The Alzheimer’s Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 controls) and one with genome-wide genotyping imputed to the Haplotype Reference Consortium panel (9,343 cases, 11,527 controls). The top findings in the discovery sample were also followed-up in the ADSP whole-genome sequenced family-based dataset (197 members of 42 EA families and 501 members of 157 CH families). We identified novel and predicted functional genetic variants in genes previously associated with AD. We also detected associations in three novel genes: IGHG3 (p = 9.8 × 10−7), an immunoglobulin gene whose antibodies interact with β-amyloid, a long non-coding RNA AC099552.4 (p = 1.2 × 10−7), and a zinc-finger protein ZNF655 (gene-based p = 5.0 × 10−6). The latter two suggest an important role for transcriptional regulation in AD pathogenesis.


BMC Proceedings | 2018

Evaluation of a phenotype imputation approach using GAW20 simulated data

Yuning Chen; Gina M. Peloso; Josée Dupuis

Statistical power, which is the probability of correctly rejecting a false null hypothesis, is a limitation of genome-wide association studies (GWAS). Sample size is a major component of statistical power that can be easily affected by missingness in phenotypic data and restrain the ability to detect associated single-nucleotide polymorphisms (SNPs) with small effect sizes. Although some phenotypes are hard to collect because of cost and loss to follow-up, correlated phenotypes that are easily collected can be leveraged for association analysis. In this paper, we evaluate a phenotype imputation method that incorporates family structure and correlation between multiple phenotypes using GAW20 simulated data. The distribution of missing values is derived using information contained in the missing sample’s relatives and additional correlated phenotypes. We show that this imputation method can improve power in the association analysis compared with excluding observations with missing data, while achieving the correct Type I error rate.We also examine factors that may affect the imputation accuracy.


European Journal of Human Genetics | 2016

Association of the IGF1 gene with fasting insulin levels

Sara M. Willems; Belinda K. Cornes; Jennifer A. Brody; Alanna C. Morrison; Leonard Lipovich; Marco Dauriz; Yuning Chen; Ching-Ti Liu; Denis Rybin; Richard A. Gibbs; Donna M. Muzny; James S. Pankow; Bruce M. Psaty; Eric Boerwinkle; Jerome I. Rotter; David S. Siscovick; Robert C. Kaplan; Aaron Isaacs; Josée Dupuis; Cornelia M. van Duijn; James B. Meigs

Insulin-like growth factor 1 (IGF-I) has been associated with insulin resistance. Genome-wide association studies (GWASs) of fasting insulin (FI) identified single-nucleotide variants (SNVs) near the IGF1 gene, raising two hypotheses: (1) these associations are mediated by IGF-I levels and (2) these noncoding variants either tag other functional variants in the region or are directly functional. In our study, analyses including 5141 individuals from population-based cohorts suggest that FI associations near IGF1 are not mediated by IGF-I. Analyses of targeted sequencing data in 3539 individuals reveal a large number of novel rare variants at the IGF1 locus and show a FI association with a subset of rare nonsynonymous variants (PSKAT=5.7 × 10−4). Conditional analyses suggest that this association is partly explained by the GWAS signal and the presence of a residual independent rare variant effect (Pconditional=0.019). Annotation using ENCODE data suggests that the GWAS variants may have a direct functional role in insulin biology. In conclusion, our study provides insight into variation present at the IGF1 locus and into the genetic architecture underlying FI levels, suggesting that FI associations of SNVs near IGF1 are not mediated by IGF-I and suggesting a role for both rare nonsynonymous and common functional variants in insulin biology.


Alzheimers & Dementia | 2016

RARE DELETERIOUS AND LOSS-OF-FUNCTION VARIANTS IN OPRL1 AND GAS2L2 CONTRIBUTE TO THE RISK OF LATE-ONSET ALZHEIMER’S DISEASE: ALZHEIMER’S DISEASE SEQUENCING PROJECT CASE-CONTROL STUDY

Xueqiu Jian; Joshua C. Bis; Brian W. Kunkle; Kara Hamilton; Gary W. Beecham; William S. Bush; William Salerno; Dan Lancour; Yiyi Ma; Yuning Chen; Anita L. DeStefano; Josée Dupuis; Eric Boerwinkle; Gerard D. Schellenberg; Sudha Seshadri; Adam C. Naj; Myriam Fornage; Lindsay A. Farrer

P1-018 RARE DELETERIOUS AND LOSS-OF-FUNCTION VARIANTS IN OPRL1 AND GAS2L2 CONTRIBUTE TO THE RISK OF LATE-ONSETALZHEIMER’S DISEASE: ALZHEIMER’S DISEASE SEQUENCING PROJECT CASE-CONTROL STUDY Xueqiu Jian, Joshua C. Bis, Brian W. Kunkle, Kara L. Hamilton, Gary W. Beecham, William S. Bush, William Salerno, Dan Lancour, Yiyi Ma, Yuning Chen, Anita L. DeStefano, Josee Dupuis, Eric Boerwinkle, Gerard D. Schellenberg, Sudha Seshadri, Adam C. Naj, Myriam Fornage, Lindsay A. Farrer, the Alzheimer’s Disease Sequencing Project, University of Texas Health Science Center at Houston, Houston, TX, USA; University of Washington, Seattle, WA, USA; University of Miami Miller School of Medicine, Miami, FL, USA; Case Western Reserve University, Cleveland, OH, USA; 5 Baylor College of Medicine, Houston, TX, USA; Boston University, Boston, MA, USA; Boston University School of Public Health, Boston, MA, USA; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Contact e-mail: [email protected]


The New England Journal of Medicine | 1989

Diagnosis of cystinosis with use of placenta.

Smith Ml; K F Clark; Davis Se; Greene Aa; Marcusson Eg; Yuning Chen; Julie A. Schneider


Archive | 2010

Cardiovascular Risk Factors Are Increased in People Reporting Chronic Pain Symptoms

Kate L. Holliday; Wendy Thomson; Anushka Soni; Kirsten M. White; Tim D. Spector; Eli A. Stahl; G. Xie; Jane Worthington; Suzanne M. M. Verstappen; Deborah Symmons; Suzanne Verstappen; Paddy Wilson; Simona Ursu; Lucy R. Wedderburn; John McBeth; Lyndsey M. Goulston; A Kiran; M K Javaid; Deborah J. Hart; N K Arden; Stephen Eyre; Anne Hinks; Anne Barton; Edward Flynn; Annette Lee; Jonathan S. Coblyn; Blair H. Smith; Leonid Padyukov; R. Chen; Katherine A. Siminovitch


Alzheimers & Dementia | 2018

STOP-GAIN VARIANT IN MICROGLIA-EXPRESSED GENE GMIP IS ASSOCIATED WITH EARLY-ONSET ALZHEIMER’S DISEASE

Raiyan R. Khan; Andre Altmann; Valerio Napolioni; Yongha Kim; Rita Guerreiro; Jose T. Bras; Susana Carmona; Miguel Tábuas Pereira; Isabel Santana; John Hardy; Simon Mead; Carlos Cruchaga; Maria Victoria Fernandez; Henne Holstege; Wiesje M. van der Flier; Marc Hulsman; Sven J. van der Lee; Yuning Chen; Joshua C. Bis; Lenore J. Launer; Cornelia M. van Duijn; Adam C. Naj; Gerard D. Schellenberg; Giovanni Coppola; Jason A. Chen; Sudha Seshadri; J. Nicholas Cochran; Richard H. Myers; Ethan G. Geier; Jennifer S. Yokoyama


Diabetologia | 2017

Gene-diet interaction analysis, fine mapping and genomic annotation of the FADS1-2-3 gene cluster reveals regulatory potential in diabetes

Paul W. Franks; Yuning Chen; Angela C. Estampador; Maria Keller; Alaitz Poveda; Jonathan Dalla-Riva; Frida Renström; Azra Kurbasic; Tibor V. Varga

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Joshua C. Bis

University of Washington

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Eric Boerwinkle

University of Texas Health Science Center at Houston

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Xueqiu Jian

University of Texas Health Science Center at Houston

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Adam C. Naj

University of Pennsylvania

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Bruce M. Psaty

University of Washington

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Carlos Cruchaga

Washington University in St. Louis

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