Manuela Uda
National Research Council
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Publication
Featured researches published by Manuela Uda.
Nature Genetics | 2009
Arne Pfeufer; Serena Sanna; Dan E. Arking; Martina Müller; Vesela Gateva; Christian Fuchsberger; Georg B. Ehret; Marco Orru; Cristian Pattaro; Anna Köttgen; Siegfried Perz; Gianluca Usala; Maja Barbalic; Man Li; Benno Pütz; Angelo Scuteri; Ronald J. Prineas; Moritz F. Sinner; Christian Gieger; Samer S. Najjar; W.H. Linda Kao; Thomas W. Mühleisen; Mariano Dei; Christine Happle; Stefan Möhlenkamp; Laura Crisponi; Raimund Erbel; Karl-Heinz Jöckel; Silvia Naitza; Gerhard Steinbeck
The QT interval, a measure of cardiac repolarization, predisposes to ventricular arrhythmias and sudden cardiac death (SCD) when prolonged or shortened. A common variant in NOS1AP is known to influence repolarization. We analyze genome-wide data from five population-based cohorts (ARIC, KORA, SardiNIA, GenNOVA and HNR) with a total of 15,842 individuals of European ancestry, to confirm the NOS1AP association and identify nine additional loci at P < 5 × 10−8. Four loci map near the monogenic long-QT syndrome genes KCNQ1, KCNH2, SCN5A and KCNJ2. Two other loci include ATP1B1 and PLN, genes with established electrophysiological function, whereas three map to RNF207, near LITAF and within NDRG4-GINS3-SETD6-CNOT1, respectively, all of which have not previously been implicated in cardiac electrophysiology. These results, together with an accompanying paper from the QTGEN consortium, identify new candidate genes for ventricular arrhythmias and SCD.
PLOS Genetics | 2005
Siguang Li; Serena Sanna; Andrea Maschio; Fabio Busonero; Gianluca Usala; Antonella Mulas; Sandra Lai; Mariano Dei; Marco Orru; Giuseppe Albai; Stefania Bandinelli; David Schlessinger; Edward G. Lakatta; Angelo Scuteri; Samer S. Najjar; Jack M. Guralnik; Silvia Naitza; Laura Crisponi; Antonio Cao; Gonçalo R. Abecasis; Luigi Ferrucci; Manuela Uda; Wei-Min Chen; Ramaiah Nagaraja
High serum uric acid levels elevate pro-inflammatory–state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 × 10−16), along with eight others (p = 7.75 × 10−16 to 6.05 × 10−11). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values.
Molecular Psychiatry | 2010
Antonio Terracciano; Serena Sanna; Manuela Uda; Barbara Deiana; Gianluca Usala; Fabio Busonero; Andrea Maschio; Matthew Scally; Nicholas S. Patriciu; Wei-Min Chen; Marijn A. Distel; Eline Slagboom; D.I. Boomsma; Sandra Villafuerte; E. Śliwerska; Margit Burmeister; Najaf Amin; A. C. J. W. Janssens; C. M. van Duijn; David Schlessinger; Gonçalo R. Abecasis; Paul T. Costa
Personality traits are summarized by five broad dimensions with pervasive influences on major life outcomes, strong links to psychiatric disorders and clear heritable components. To identify genetic variants associated with each of the five dimensions of personality we performed a genome-wide association (GWA) scan of 3972 individuals from a genetically isolated population within Sardinia, Italy. On the basis of the analyses of 362 129 single-nucleotide polymorphisms we found several strong signals within or near genes previously implicated in psychiatric disorders. They include the association of neuroticism with SNAP25 (rs362584, P=5 × 10−5), extraversion with BDNF and two cadherin genes (CDH13 and CDH23; Ps<5 × 10−5), openness with CNTNAP2 (rs10251794, P=3 × 10−5), agreeableness with CLOCK (rs6832769, P=9 × 10−6) and conscientiousness with DYRK1A (rs2835731, P=3 × 10−5). Effect sizes were small (less than 1% of variance), and most failed to replicate in the follow-up independent samples (N up to 3903), though the association between agreeableness and CLOCK was supported in two of three replication samples (overall P=2 × 10−5). We infer that a large number of loci may influence personality traits and disorders, requiring larger sample sizes for the GWA approach to confidently identify associated genetic variants.
Molecular Psychiatry | 2012
M.H.M. de Moor; Paul T. Costa; Antonio Terracciano; Robert F. Krueger; E.J.C. de Geus; T Toshiko; Brenda W. J. H. Penninx; Tonu Esko; P. A. F. Madden; Jaime Derringer; Najaf Amin; Gonneke Willemsen; J.J. Hottenga; Marijn A. Distel; Manuela Uda; Serena Sanna; Philip Spinhoven; C. A. Hartman; Patrick F. Sullivan; Anu Realo; Jüri Allik; A. C. Heath; Michele L. Pergadia; Arpana Agrawal; Peng Lin; Richard A. Grucza; Teresa Nutile; Marina Ciullo; Dan Rujescu; Ina Giegling
Personality can be thought of as a set of characteristics that influence peoples thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17 375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ∼2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P=2.8 × 10−8 and 3.1 × 10−8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 × 10−8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.
Nature Genetics | 2011
Joshua C. Bis; Maryam Kavousi; Nora Franceschini; Aaron Isaacs; Gonçalo R. Abecasis; Ulf Schminke; Wendy S. Post; Albert V. Smith; L. Adrienne Cupples; Hugh S. Markus; Reinhold Schmidt; Jennifer E. Huffman; Terho Lehtimäki; Jens Baumert; Thomas Münzel; Susan R. Heckbert; Abbas Dehghan; Kari E. North; Ben A. Oostra; Steve Bevan; Eva Maria Stoegerer; Caroline Hayward; Olli T. Raitakari; Christa Meisinger; Arne Schillert; Serena Sanna; Henry Völzke; Yu Ching Cheng; Bolli Thorsson; Caroline S. Fox
Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10−8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.
Nature Genetics | 2010
Serena Sanna; Maristella Pitzalis; Magdalena Zoledziewska; Ilenia Zara; Carlo Sidore; Raffaele Murru; Michael B. Whalen; Fabio Busonero; Andrea Maschio; Gianna Costa; Maria Cristina Melis; Francesca Deidda; Fausto Pier'Angelo Poddie; Laura Cornelia Clotilde Morelli; Gabriele Farina; Yun Li; Mariano Dei; Sandra Lai; Antonella Mulas; Gianmauro Cuccuru; E. Porcu; Liming Liang; Patrizia Zavattari; Loredana Moi; Elisa Deriu; M. Francesca Urru; Michele Bajorek; Maria Anna Satta; Eleonora Cocco; Paola Ferrigno
A genome-wide association scan of ∼6.6 million genotyped or imputed variants in 882 Sardinian individuals with multiple sclerosis (cases) and 872 controls suggested association of CBLB gene variants with disease, which was confirmed in 1,775 cases and 2,005 controls (rs9657904, overall P = 1.60 × 10−10, OR = 1.40). CBLB encodes a negative regulator of adaptive immune responses, and mice lacking the ortholog are prone to experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis.
American Journal of Human Genetics | 2007
Lenuta Balaci; Maria Cristina Spada; Nazario Olla; Gabriella Sole; Laura Loddo; Francesca Anedda; Silvia Naitza; Maria Antonietta Zuncheddu; Andrea Maschio; Daniele Altea; Manuela Uda; Sabrina Pilia; Serena Sanna; Marco Masala; Laura Crisponi; Matilde Fattori; Marcella Devoto; Silvia Doratiotto; Stefania Rassu; Simonetta Mereu; Enrico Giua; Natalina Graziella Cadeddu; Roberto Atzeni; Umberto Pelosi; Adriano Corrias; Roberto Perra; Pier Luigi Torrazza; Pietro Pirina; Francesco Ginesu; Silvano Marcias
Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and >100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma.
Translational Psychiatry | 2011
Antonio Terracciano; Tonu Esko; Angelina R. Sutin; M.H.M. de Moor; Osorio Meirelles; Gu Zhu; Toshiko Tanaka; Ina Giegling; Teresa Nutile; Anu Realo; Jüri Allik; Narelle K. Hansell; Margaret J. Wright; Grant W. Montgomery; Gonneke Willemsen; J.J. Hottenga; Marion Friedl; Daniela Ruggiero; Rossella Sorice; Serena Sanna; Alessandra Cannas; Katri Räikkönen; Elisabeth Widen; Aarno Palotie; Johan G. Eriksson; F. Cucca; Robert F. Krueger; Jari Lahti; Michelle Luciano; Jordan W. Smoller
The tendency to seek stimulating activities and intense sensations define excitement-seeking, a personality trait akin to some aspects of sensation-seeking. This trait is a central feature of extraversion and is a component of the multifaceted impulsivity construct. Those who score high on measures of excitement-seeking are more likely to smoke, use other drugs, gamble, drive recklessly, have unsafe/unprotected sex and engage in other risky behaviors of clinical and social relevance. To identify common genetic variants associated with the Excitement-Seeking scale of the Revised NEO Personality Inventory, we performed genome-wide association studies in six samples of European ancestry (N=7860), and combined the results in a meta-analysis. We identified a genome-wide significant association between the Excitement-Seeking scale and rs7600563 (P=2 × 10−8). This single-nucleotide polymorphism maps within the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene, which encodes for a brain-expressed α-catenin critical for synaptic contact. The effect of rs7600563 was in the same direction in all six samples, but did not replicate in additional samples (N=5105). The results provide insight into the genetics of excitement-seeking and risk-taking, and are relevant to hyperactivity, substance use, antisocial and bipolar disorders.
PLOS Genetics | 2010
Angelo Scuteri; Serena Sanna; Wm Chen; Manuela Uda; Giuseppe Albai; James B. Strait; Samer S. Najjar; Ramaiah Nagaraja; Marco Orru; Gianluca Usala; Mariano Dei; Sandra Lai; Andrea Maschio; Fabio Busonero; Antonella Mulas; Gb Ehret; Aa Fink; Ab Weder; Rs Cooper; Pilar Galan; Aravinda Chakravarti; David Schlessinger; Antonio Cao; Edward G. Lakatta; Gr Abecasis
Genomics | 2004
Laura Crisponi; Manuela Uda; Manila Deiana; Angela Loi; Ramaiah Nagaraja; Francesca Chiappe; David Schlessinger; Antonio Cao; Giuseppe Pilia