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Expression quantitative trait loci ( eQTLs )

Hélène Quach, Maxime Rotival, Julien Pothlichet, Yong-Hwee Eddie Loh, Michael Dannemann, Nora Zidane, Guillaume Laval, Etienne Patin, Christine Harmant, Marie Lopez, Matthieu Deschamps, Nadia Naffakh, Darragh Duffy, Anja Coen, Geert Leroux-Roels, Frederic Clément, Anne Boland, Jean-François Deleuze, Janet Kelso, Matthew L Albert, Lluis Quintana-Murci
Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli-ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus-and mapped expression quantitative trait loci (eQTLs)...
October 20, 2016: Cell
Eun Yong Kang, Lisa Martin, Serghei Mangul, Warin Isvilanonda, Jennifer Zou, Eyal Ben-David, Buhm Han, Aldons J Lusis, Sagiv Shifman, Eleazar Eskin
The study of the genetics of gene expression is of considerable importance to understanding the nature of common, complex diseases. The most widely applied approach to identifying relationships between genetic variation and gene expression is the expression quantitative trait loci (eQTL) approach. Here we increase the computational power of eQTL with an alternative and complementary approach based on analyzing allele specific expression (ASE). We design a novel analytical method to identify cis-acting regulatory variants based on genome sequencing and measurements of ASE from RNA-seq data...
October 7, 2016: Genetics
Aharon Nachshon, Hanifa J Abu-Toamih Atamni, Yael Steuerman, Roa'a Sheikh-Hamed, Alexandra Dorman, Richard Mott, Juliane C Dohm, Hans Lehrach, Marc Sultan, Ron Shamir, Sascha Sauer, Heinz Himmelbauer, Fuad A Iraqi, Irit Gat-Viks
A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions...
2016: Frontiers in Genetics
Ryosuke Kita, Hunter B Fraser
Sun-exposure is a key environmental variable in the study of human evolution. Several skin-pigmentation genes serve as classical examples of positive selection, suggesting that sun-exposure has significantly shaped worldwide genomic variation. Here we investigate the interaction between genetic variation and sun-exposure, and how this impacts gene expression regulation. Using RNA-Seq data from 607 human skin samples, we identified thousands of transcripts that are differentially expressed between sun-exposed skin and non-sun-exposed skin...
October 2016: PLoS Genetics
Hanseol Kim, Jihye Ryu, Chaeyoung Lee
A genome-wide association study was conducted to identify expression quantitative trait loci (eQTL) for human telomerase.We tested the genetic associations of nucleotide variants with expression of the genes encoding human telomerase reverse transcriptase (hTERT) and telomerase RNA components (TERC) in lymphoblastoid cell lines derived from 373 Europeans.Our results revealed 6 eQTLs associated with hTERT (P < 5 × 10). One eQTL (rs17755753) was located in the intron 1 of the gene encoding R-spondin-3 (RSPO3), a well-known Wnt signaling regulator...
October 2016: Medicine (Baltimore)
Jing-Woei Li, Heung-Man Lee, Ying Wang, Amy Hin-Yan Tong, Kevin Y Yip, Stephen Kwok-Wing Tsui, Si Lok, Risa Ozaki, Andrea O Luk, Alice P S Kong, Wing-Yee So, Ronald C W Ma, Juliana C N Chan, Ting-Fung Chan
Protein interactions play significant roles in complex diseases. We analyzed peripheral blood mononuclear cells (PBMC) transcriptome using a multi-method strategy. We constructed a tissue-specific interactome (T2Di) and identified 420 molecular signatures associated with T2D-related comorbidity and symptoms, mainly implicated in inflammation, adipogenesis, protein phosphorylation and hormonal secretion. Apart from explaining the residual associations within the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) study, the T2Di signatures were enriched in pathogenic cell type-specific regulatory elements related to fetal development, immunity and expression quantitative trait loci (eQTL)...
October 18, 2016: Scientific Reports
Wanqing Liu, Quentin M Anstee, Xiaoliang Wang, Samer Gawrieh, Eric R Gamazon, Shaminie Athinarayanan, Yang-Lin Liu, Rebecca Darlay, Heather J Cordell, Ann K Daly, Chris P Day, Naga Chalasani
The increased expression of PNPLA3(148M) leads to hepatosteatosis in mice. This study aims to investigate the genetic control of hepatic PNPLA3 transcription and to explore its impact on NAFLD risk in humans. Through a locus-wide expression quantitative trait loci (eQTL) mapping in two human liver sample sets, a PNPLA3 intronic SNP, rs139051 A>G was identified as a significant eQTL (p = 6.6×10(-8)) influencing PNPLA3 transcription, with the A allele significantly associated with increased PNPLA3 mRNA. An electrophoresis mobility shift assay further demonstrated that the A allele has enhanced affinity to nuclear proteins than the G allele...
October 13, 2016: Aging
Aida Moreno-Moral, Enrico Petretto
Complementary to traditional gene mapping approaches used to identify the hereditary components of complex diseases, integrative genomics and systems genetics have emerged as powerful strategies to decipher the key genetic drivers of molecular pathways that underlie disease. Broadly speaking, integrative genomics aims to link cellular-level traits (such as mRNA expression) to the genome to identify their genetic determinants. With the characterization of several cellular-level traits within the same system, the integrative genomics approach evolved into a more comprehensive study design, called systems genetics, which aims to unravel the complex biological networks and pathways involved in disease, and in turn map their genetic control points...
October 1, 2016: Disease Models & Mechanisms
Paola G Bronson, Diana Chang, Tushar Bhangale, Michael F Seldin, Ward Ortmann, Ricardo C Ferreira, Elena Urcelay, Luis Fernández Pereira, Javier Martin, Alessandro Plebani, Vassilios Lougaris, Vanda Friman, Tomáš Freiberger, Jiri Litzman, Vojtech Thon, Qiang Pan-Hammarström, Lennart Hammarström, Robert R Graham, Timothy W Behrens
Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 × 10(-8)) loci and association with a rare IFIH1 variant (p.Ile923Val). Peak new variants (PVT1, P = 4.3 × 10(-11); ATG13-AMBRA1, P = 6.7 × 10(-10); AHI1, P = 8.4 × 10(-10); CLEC16A, P = 1.4 × 10(-9)) overlapped with autoimmune markers (3/4) and correlated with 21 putative regulatory variants, including expression quantitative trait loci (eQTLs) for AHI1 and DEXI and DNase hypersensitivity sites in FOXP3(+) regulatory T cells...
October 10, 2016: Nature Genetics
Ying Jin, Genevieve Andersen, Daniel Yorgov, Tracey M Ferrara, Songtao Ben, Kelly M Brownson, Paulene J Holland, Stanca A Birlea, Janet Siebert, Anke Hartmann, Anne Lienert, Nanja van Geel, Jo Lambert, Rosalie M Luiten, Albert Wolkerstorfer, J P Wietze van der Veen, Dorothy C Bennett, Alain Taïeb, Khaled Ezzedine, E Helen Kemp, David J Gawkrodger, Anthony P Weetman, Sulev Kõks, Ele Prans, Külli Kingo, Maire Karelson, Margaret R Wallace, Wayne T McCormack, Andreas Overbeck, Silvia Moretti, Roberta Colucci, Mauro Picardo, Nanette B Silverberg, Mats Olsson, Yan Valle, Igor Korobko, Markus Böhm, Henry W Lim, Iltefat Hamzavi, Li Zhou, Qing-Sheng Mi, Pamela R Fain, Stephanie A Santorico, Richard A Spritz
Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication...
October 10, 2016: Nature Genetics
Ivan Kel, Zisong Chang, Nadia Galluccio, Margherita Romeo, Stefano Beretta, Luisa Diomede, Alessandra Mezzelani, Luciano Milanesi, Christoph Dieterich, Ivan Merelli
The interpretation of genome-wide association study is difficult, as it is hard to understand how polymorphisms can affect gene regulation, in particular for trans-regulatory elements located far from their controlling gene. Using RNA or protein expression data as phenotypes, it is possible to correlate their variations with specific genotypes. This technique is usually referred to as expression Quantitative Trait Loci (eQTLs) analysis and only few packages exist for the integration of genotype patterns and expression profiles...
September 22, 2016: Molecular BioSystems
Marc-Emmanuel Dumas, Céline Domange, Sophie Calderari, Andrea Rodríguez Martínez, Rafael Ayala, Steven P Wilder, Nicolas Suárez-Zamorano, Stephan C Collins, Robert H Wallis, Quan Gu, Yulan Wang, Christophe Hue, Georg W Otto, Karène Argoud, Vincent Navratil, Steve C Mitchell, John C Lindon, Elaine Holmes, Jean-Baptiste Cazier, Jeremy K Nicholson, Dominique Gauguier
BACKGROUND: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus occurs through complex organ-specific cellular mechanisms and networks contributing to impaired insulin secretion and insulin resistance. Genome-wide gene expression profiling systems can dissect the genetic contributions to metabolome and transcriptome regulations. The integrative analysis of multiple gene expression traits and metabolic phenotypes (i.e., metabotypes) together with their underlying genetic regulation remains a challenge...
September 30, 2016: Genome Medicine
Bodo Brand, Markus O Scheinhardt, Juliane Friedrich, Daisy Zimmer, Norbert Reinsch, Siriluck Ponsuksili, Manfred Schwerin, Andreas Ziegler
BACKGROUND: The importance of the adrenal gland in regard to lactation and reproduction in cattle has been recognized early. Caused by interest in animal welfare and the impact of stress on economically important traits in farm animals the adrenal gland and its function within the stress response is of increasing interest. However, the molecular mechanisms and pathways involved in stress-related effects on economically important traits in farm animals are not fully understood. Gene expression is an important mechanism underlying complex traits, and genetic variants affecting the transcript abundance are thought to influence the manifestation of an expressed phenotype...
October 6, 2016: BMC Genetics
Guo-Dong Li, Dong Wang, Deng-Feng Zhang, Qun Xiang, Jia-Qi Feng, Xiao-An Li, Yu-Ye Li, Yong-Gang Yao
BACKGROUND: Previous genome-wide association study (GWAS) identified two new leprosy associated loci (1p31.3 [rs3762318] and 6q24.3 [rs2275606]). However, there were insufficient validations in independent populations. OBJECTIVE: To validate the association and to map the potentially causal variants/genes underlying the association between the confirmed GWAS hit and leprosy. METHODS: We genotyped 10 variants in the regions encompassing the two loci in 1110 Han Chinese subjects with and without leprosy, followed by expression quantitative trait loci (eQTL), mRNA expression profiling, and network analysis...
September 28, 2016: Journal of Dermatological Science
Y-M Zhang, X-J Zhou, F-J Cheng, Y-Y Qi, P Hou, M-H Zhao, H Zhang
OBJECTIVES: Polymorphisms of IKAROS family zinc finger 1 (IKZF1) have been found to be associated with systemic lupus erythematosus (SLE) by genome-wide association studies (GWAS). The aim of the current study was to investigate the association between IKZF1 functional variants and lupus nephritis (LN) in a northern Han Chinese population and analyse their relationship with clinical and pathological phenotypes in LN. METHOD: The association between IKZF1 functional variants and LN was analysed for the lead variant rs1456896 with both GWAS and expression quantitative trait loci (eQTL) top hits in 500 LN patients and 500 healthy controls...
August 16, 2016: Scandinavian Journal of Rheumatology
S-W Chang, C W McDonough, Y Gong, T A Johnson, T Tsunoda, E R Gamazon, M A Perera, A Takahashi, T Tanaka, M Kubo, C J Pepine, J A Johnson, R M Cooper-DeHoff
We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a β-blocker-based strategy (β-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP*treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls)...
September 27, 2016: Pharmacogenomics Journal
Joanna M Peloquin, Gautam Goel, Lingjia Kong, Hailiang Huang, Talin Haritunians, R Balfour Sartor, Mark J Daly, Rodney D Newberry, Dermot P McGovern, Vijay Yajnik, Sergio A Lira, Ramnik J Xavier
GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn's disease or ulcerative colitis and from healthy controls...
2016: JCI Insight
Anna Puig-Oliveras, Manuel Revilla, Anna Castelló, Ana I Fernández, Josep M Folch, Maria Ballester
The aim of this work is to better understand the genetic mechanisms determining two complex traits affecting porcine meat quality: intramuscular fat (IMF) content and its fatty acid (FA) composition. With this purpose, expression Genome-Wide Association Study (eGWAS) of 45 lipid-related genes associated with meat quality traits in swine muscle (Longissimus dorsi) of 114 Iberian × Landrace backcross animals was performed. The eGWAS identified 241 SNPs associated with 11 genes: ACSM5, CROT, FABP3, FOS, HIF1AN, IGF2, MGLL, NCOA1, PIK3R1, PLA2G12A and PPARA...
2016: Scientific Reports
Ence Yang, Gang Wang, Jizhou Yang, Beiyan Zhou, Yanan Tian, James J Cai
Increasing evidence shows that, like phenotypic mean, phenotypic variance is also genetically determined, but the underlying mechanisms of genetic control over the variance remain obscure. Here, we conducted variance-association mapping analyses to identify expression variability QTLs (evQTLs), i.e., genomic loci associated with gene expression variance, in humans. We discovered that common genetic variations may contribute to increasing gene expression variability via two distinct modes of action-epistasis and destabilization...
September 20, 2016: Human Molecular Genetics
Julio D Duarte, Ankit A Desai, Justin R Sysol, Taimur Abbasi, Amit R Patel, Roberto M Lang, Akash Gupta, Joe G N Garcia, Victor R Gordeuk, Roberto F Machado
BACKGROUND: Diastolic dysfunction is common in sickle cell disease (SCD), and is associated with an increased risk of mortality. However, the molecular pathogenesis underlying this development is poorly understood. The aim of this study was to identify a gene expression profile that is associated with diastolic function in SCD, potentially elucidating molecular mechanisms behind diastolic dysfunction development. METHODS: Diastolic function was measured via echocardiography in 65 patients with SCD from two independent study populations...
2016: PloS One
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