ORCID Profile
0000-0002-5363-3886
Current Organisations
Human Technopole
,
The University of Edinburgh
,
Università degli Studi di Trieste Dipartimento di Scienze Mediche Chirurgiche e della Salute
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 07-2015
DOI: 10.1038/NATURE14618
Publisher: Springer Science and Business Media LLC
Date: 23-07-2018
Publisher: Cold Spring Harbor Laboratory
Date: 09-04-2013
Abstract: Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type–restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type–specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type–restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits.
Publisher: Springer Science and Business Media LLC
Date: 25-11-2027
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1038/NATURE11677
Publisher: Public Library of Science (PLoS)
Date: 19-07-2012
Publisher: Springer Science and Business Media LLC
Date: 31-10-2019
DOI: 10.1038/S41467-019-12283-6
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients ( F ROH ) for .4 million in iduals, we show that F ROH is significantly associated ( p 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of F ROH are confirmed within full-sibling pairs, where the variation in F ROH is independent of all environmental confounding.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Public Library of Science (PLoS)
Date: 17-04-2014
Publisher: Springer Science and Business Media LLC
Date: 14-01-2019
Publisher: Oxford University Press (OUP)
Date: 27-07-2012
DOI: 10.1093/HMG/DDS304
Publisher: Springer Science and Business Media LLC
Date: 22-08-2016
DOI: 10.1038/NG.3643
Publisher: Springer Science and Business Media LLC
Date: 28-09-2015
DOI: 10.1038/NG.3412
Publisher: Proceedings of the National Academy of Sciences
Date: 31-10-2016
Abstract: In iduals with more education tend to live longer. Genetic variants have been discovered that predict educational attainment. We tested whether a “polygenic score” based on these genetic variants could make predictions about people’s lifespan. We used data from three cohort studies (including ,000 participants) to examine the link between offspring polygenic score for education and parental longevity. Across the studies, we found that participants with more education-linked genetic variants had longer-living parents compared with those with the lowest genetic education scores, those with the highest scores had parents who lived on average 6 months longer. This finding suggests the hypothesis that part of the ultimate explanation for the extended longevity of better-educated people is an underlying, quantifiable, genetic propensity.
Publisher: Springer Science and Business Media LLC
Date: 13-10-2017
DOI: 10.1038/S41467-017-00934-5
Abstract: Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents’ survival, we discover two regions associated with longevity ( HLA-DQA1/DRB1 and LPA ). We also validate previous suggestions that APOE , CHRNA3/5 , CDKN2A/B , SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.
Publisher: Springer Science and Business Media LLC
Date: 23-12-2012
DOI: 10.1038/NG.2500
Publisher: Springer Science and Business Media LLC
Date: 11-05-2016
DOI: 10.1038/NATURE17671
Location: United Kingdom of Great Britain and Northern Ireland
Location: Italy
No related grants have been discovered for Nicola Pirastu.