ORCID Profile
0000-0002-7414-1995
Current Organisations
Institute of Subtropical Agriculture Chinese Academy of Sciences
,
Università degli Studi di Sassari
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Publisher: Oxford University Press (OUP)
Date: 07-1996
DOI: 10.1093/HMG/5.7.1071
Abstract: Linkage analysis of type 1 diabetes sib pair families (n = 334) has suggested two separate regions of human chromosome 6q are linked to disease (designated IDDM5 and IDDM8). To test if these are false positive results, all available sib pair families (n = 429) were typed using a 92% informative map of chromosome 6q and multipoint analysis. The two regions still showed positive evidence of linkage, most notably the proterminal region, 6q27, corresponding to IDDM8 (MLS = 2.57, p = 0.0006 lambda s = 1.17). In addition, some evidence of transmission disequilibrium was seen with marker a046xa9 (IDDM5).
Publisher: Informa UK Limited
Date: 1996
DOI: 10.3109/10425179609015641
Abstract: To examine the dose-response associations between total physical activity, different intensity of physical activity, and all-cause mortality in patients with chronic kidney disease (CKD). PubMed, Embase, Web of Science, and the Cochrane library will be searched from inception to June 2022. Only cohort studies assessing physical activity associations with all-cause mortality among CKD patients will be considered for inclusion. The quality of included cohort studies will be evaluated according to the Newcastle-Ottawa Scale (NOS). The robust error meta-regression (REMR) model will be used to establish dose-response relationships between physical activity and mortality. Additional statistical analysis including Egger's test, subgroup analysis, sensitivity analysis. The strengths of evidence will be evaluated with the Grading of Recommendation, Assessment, Development, and Evaluation approach. Ethics approval is not required as no private information from in iduals is collected. CRD 42021283630.
Publisher: Springer Science and Business Media LLC
Date: 23-07-2018
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1038/NATURE11677
Publisher: Springer Science and Business Media LLC
Date: 31-10-2012
DOI: 10.1038/NATURE11632
Publisher: American Diabetes Association
Date: 11-1998
Publisher: Elsevier BV
Date: 06-2017
Publisher: Springer Science and Business Media LLC
Date: 26-04-2017
DOI: 10.1038/NCOMMS14977
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study s le. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Publisher: Springer Science and Business Media LLC
Date: 23-11-2016
DOI: 10.1038/NCOMMS13357
Abstract: Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain % of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5 / C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
Publisher: American Geophysical Union (AGU)
Date: 04-2023
DOI: 10.1029/2022WR033566
Abstract: Water ages in plant transpiration reveal important processes of water dynamics in soil‐plant‐atmosphere continuum, which is regulated by water variability and availability in both precipitation inputs and root zone. However, the impacts of climate patterns and rooting depth on water age dynamics in transpiration are inadequately investigated. In this study, variations in root‐zone water replenishment are estimated based on stable isotope compositions of precipitation and plant xylem water, and a piecewise linear mixing water age model is employed to quantify water ages in plant transpiration under five different climates. The results show that water ages in transpiration are very dynamic in all climates with a range between 1 and 229 days. Water replenishments in the root‐zone reveal whether and how much precipitation enters the root zone. Climate patterns control median (mean) water age in plant transpiration but modified by rooting depth. In wet climates, plants mainly rely on water source that originates from precipitation in the current month (accounting for about 60% on average of their water sources), while plants in dry climates largely rely on water source that originates from precipitation fallen on previous months/seasons. These indicate that climate has profound impacts on plant water source by regulating precipitation inputs, root zone water storage and residence time, and evapotranspiration. Despite the limitations of this study, our study provides an alternative way to reveal the precipitation partitioning in root‐zone and seasonal changes in plant water use of precipitation, which highlights different vegetation responses to water variability between climate types.
Publisher: Springer Science and Business Media LLC
Date: 06-03-2015
DOI: 10.1038/NCOMMS6681
Abstract: Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project ( N =2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 ( N =16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P =6.15 × 10 −9 ) and a new independent variant in PDE8B (MAF=10.4%, P =5.94 × 10 −14 ). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P =1.27 × 10 −9 ) tagging a rare TTR variant (MAF=0.4%, P =2.14 × 10 −11 ). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF %) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.
Publisher: Research Square Platform LLC
Date: 10-03-2022
DOI: 10.21203/RS.3.RS-1409164/V1
Abstract: Hypertension is a leading cause of premature death affecting more than a billion in iduals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent in iduals). We identified 2,103 independent genetic signals (P 5x10 − 8 ) for BP traits, including 113 novel loci. These associations explain ~ 40% of common SNP heritability of systolic and diastolic BP. Comparison of top versus bottom deciles of polygenic risk scores (PRS) based on these results reveal clinically meaningful differences in BP (12.9 mm Hg for systolic BP, 95% CI 11.5–14.2 mm Hg, p = 9.08×10 − 73 ) and hypertension risk (OR 5.41 95% CI 4.12 to 7.10 P = 9.71×10 − 33 ) in an independent dataset. Compared with the area under the curve (AUC) for hypertension discrimination for a model with sex, age, BMI, and genetic ancestry, adding systolic and diastolic BP PRS increased discrimination from 0.791 (95% CI = 0.781–0.801) to 0.814 (95% CI = 0.805–0.824, ∆AUC = 0.023, P = 2.27x10 − 22 ). Our transcriptome-wide association study detected 2,793 BP colocalized associations with genetically-predicted expression of 1,070 genes in five cardiovascular tissues, of which 500 are previously unreported for BP traits. These findings represent an advance in our understanding of hypertension and highlight the role of increasingly large genomic studies for development of more accurate PRS, which may inform precision health research.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2012
DOI: 10.1038/NG.2385
Publisher: Public Library of Science (PLoS)
Date: 10-2015
Publisher: Wiley
Date: 05-07-2014
DOI: 10.1002/AJMG.B.32254
Abstract: The American Psychiatric Association estimates that 3 to 7 per cent of all school aged children are diagnosed with attention deficit hyperactivity disorder (ADHD). Even after correcting for general cognitive ability, numerous studies report a negative association between ADHD and educational achievement. With polygenic scores we examined whether genetic variants that have a positive influence on educational attainment have a protective effect against ADHD. The effect sizes from a large GWA meta-analysis of educational attainment in adults were used to calculate polygenic scores in an independent s le of 12-year-old children from the Netherlands Twin Register. Linear mixed models showed that the polygenic scores significantly predicted educational achievement, school performance, ADHD symptoms and attention problems in children. These results confirm the genetic overlap between ADHD and educational achievement, indicating that one way to gain insight into genetic variants responsible for variation in ADHD is to include data on educational achievement, which are available at a larger scale.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2016
DOI: 10.1038/NG.3552
Publisher: Springer Science and Business Media LLC
Date: 31-10-2016
DOI: 10.1038/NG.3698
Publisher: Elsevier BV
Date: 06-2019
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
Publisher: Springer Science and Business Media LLC
Date: 29-04-2014
DOI: 10.1038/NCOMMS4513
Publisher: Springer Science and Business Media LLC
Date: 17-09-2018
Publisher: Springer Science and Business Media LLC
Date: 26-10-2018
DOI: 10.1038/S41467-018-06356-1
Abstract: Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 in iduals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves’ disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-06-2016
Abstract: Genome-wide study in Germans identifies four novel multiple sclerosis risk genes and confirms already known gene loci.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2020
DOI: 10.1038/S41467-020-15706-X
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry ( N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Publisher: Wiley
Date: 11-2013
DOI: 10.1002/GEPI.21760
Publisher: Springer Science and Business Media LLC
Date: 18-10-2011
DOI: 10.1038/TP.2011.42
Publisher: Public Library of Science (PLoS)
Date: 27-04-2017
Publisher: Elsevier BV
Date: 03-2012
Publisher: American Diabetes Association
Date: 09-1998
Publisher: American Medical Association (AMA)
Date: 08-2012
Publisher: American Association for the Advancement of Science (AAAS)
Date: 21-06-2013
Abstract: Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 s les, Rietveld et al. (p. 1467 , published online 30 May see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2019
DOI: 10.1038/S41380-018-0313-0
Abstract: Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P 5 × 10 −8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits ( P 5 × 10 −8 ) in the discovery s les. Ten novel SNVs, including rs12616219 near TMEM182 , were followed-up and five of them (rs462779 in REV3L , rs12780116 in CNNM2 , rs1190736 in GPR101 , rs11539157 in PJA1 , and rs12616219 near TMEM182 ) replicated at a Bonferroni significance threshold ( P 4.5 × 10 −3 ) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2 . Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
Publisher: Springer Science and Business Media LLC
Date: 04-08-2015
DOI: 10.1038/NCOMMS8756
Abstract: More than 100 loci have been identified for age at menarche by genome-wide association studies however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1 / LAMB2 / TNRC6A/TACR3/PRKAG1 ) are associated with age at menarche (minor allele frequencies 0.08–4.6% effect sizes 0.08–1.25 years per allele P × 10 −8 ). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P =9.4 × 10 −13 ) and FAAH2 (rs5914101, P =4.9 × 10 −10 ). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche ( P =2.8 × 10 −11 ), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the ‘missing heritability’ of this complex trait.
Publisher: Springer Science and Business Media LLC
Date: 22-01-2002
DOI: 10.1038/NG825
Publisher: Public Library of Science (PLoS)
Date: 07-02-2013
Publisher: Springer Science and Business Media LLC
Date: 30-04-2003
DOI: 10.1038/NATURE01621
Publisher: Springer Science and Business Media LLC
Date: 07-1998
DOI: 10.1038/995
Abstract: It is generally assumed that the male:female (M:F) ratio in patients with type 1 (insulin-dependent) diabetes mellitus (IDDM) is 1. A recent survey, however, revealed that high incidence countries (mainly European) have a high M:F ratio and low incidence ones (Asian and African) have a low M:F ratio. We have now analysed the M:F ratio according to genotype at the major locus, the major histocompatibility complex (MHC IDDM1). There are two main IDDM1 susceptibility haplotypes, HLA-DR3 and -DR4, which are present in 95% of Caucasian cases. We report here that in medium/high incidence Caucasian populations from the United States of America, United Kingdom and Sardinia (1307 cases), the bias in male incidence is largely restricted to the DR3/X category of patients (X not = DR4) with a M:F ratio of 1.7 (P=9.3x10(-7)), compared with a ratio of 1.0 in the DR4/Y category (Y DR3). This is additional evidence for significant heterogeneity between the aetiology of 'DR4-associated' and 'DR3-associated' diabetes. We analysed linkage of type 1 diabetes to chromosome X, and as expected, most of the linkage to Xp13-p11 was in the DR3/X affected sibpair families (n=97 peak multipoint MLS at DXS1068=3.5, P=2.7x10(-4) single point MLS=4.5, P=2.7x10(-5)). This is evidence for aetiological heterogeneity at the IDDM1/MHC locus and, therefore, in the search for non-MHC loci in type 1 diabetes, conditioning of linkage data by HLA type is advised.
Publisher: Springer Science and Business Media LLC
Date: 21-12-2018
Publisher: Springer Science and Business Media LLC
Date: 14-01-2019
Publisher: Springer Science and Business Media LLC
Date: 14-01-2019
Publisher: Springer Science and Business Media LLC
Date: 22-08-2016
DOI: 10.1038/NG.3643
Publisher: Springer Science and Business Media LLC
Date: 24-04-2017
DOI: 10.1038/NG.3841
Publisher: Springer Science and Business Media LLC
Date: 07-1998
DOI: 10.1038/991
Abstract: Genetic analysis of a mouse model of major histocompatability complex (MHC)-associated autoimmune type 1 (insulin-dependent) diabetes mellitus (IDDM) has shown that the disease is caused by a combination of a major effect at the MHC and at least ten other susceptibility loci elsewhere in the genome. A genome-wide scan of 93 affected sibpair families (ASP) from the UK (UK93) indicated a similar genetic basis for human type 1 diabetes, with the major genetic component at the MHC locus (IDDM1) explaining 34% of the familial clustering of the disease (lambda(s)=2.5 refs 3,4). In the present report, we have analysed a further 263 multiplex families from the same population (UK263) to provide a total UK data set of 356 ASP families (UK356). Only four regions of the genome outside IDDM1/MHC, which was still the only major locus detected, were not excluded at lambda(s)=3 and lod=-2, of which two showed evidence of linkage: chromosome 10p13-p11 (maximum lod score (MLS)=4.7, P=3x10(-6), lambda(s)=1.56) and chromosome 16q22-16q24 (MLS=3.4, P=6.5x10(-5), lambda(s)=1.6). These and other novel regions, including chromosome 14q12-q21 and chromosome 19p13-19q13, could potentially harbour disease loci but confirmation and fine mapping cannot be pursued effectively using conventional linkage analysis. Instead, more powerful linkage disequilibrium-based and haplotype mapping approaches must be used such data is already emerging for several type 1 diabetes loci detected initially by linkage.
Publisher: Elsevier BV
Date: 08-1998
DOI: 10.1086/301974
Abstract: Genomewide linkage studies of type 1 diabetes (or insulin-dependent diabetes mellitus [IDDM]) indicate that several unlinked susceptibility loci can explain the clustering of the disease in families. One such locus has been mapped to chromosome 11q13 (IDDM4). In the present report we have analyzed 707 affected sib pairs, obtaining a peak multipoint maximum LOD score (MLS) of 2.7 (lambda(s)=1.09) with linkage (MLS>=0.7) extending over a 15-cM region. The problem is, therefore, to fine map the locus to permit structural analysis of positional candidate genes. In a two-stage approach, we first scanned the 15-cM linked region for increased or decreased transmission, from heterozygous parents to affected siblings in 340 families, of the three most common alleles of each of 12 microsatellite loci. One of the 36 alleles showed decreased transmission (50% expected, 45.1% observed [P=.02, corrected P=.72]) at marker D11S1917. Analysis of an additional 1,702 families provided further support for negative transmission (48%) of D11S1917 allele 3 to affected offspring and positive transmission (55%) to unaffected siblings (test of heterogeneity P=3x10-4, corrected P=. 01]). A second polymorphic marker, H0570polyA, was isolated from a cosmid clone containing D11S1917, and genotyping of 2,042 families revealed strong linkage disequilibrium between the two markers (15 kb apart), with a specific haplotype, D11S1917*03-H0570polyA*02, showing decreased transmission (46.4%) to affected offspring and increased transmission (56.6%) to unaffected siblings (test of heterogeneity P=1.5x10-6, corrected P=4.3x10-4). These results not only provide sufficient justification for analysis of the gene content of the D11S1917 region for positional candidates but also show that, in the mapping of genes for common multifactorial diseases, analysis of both affected and unaffected siblings is of value and that both predisposing and nonpredisposing alleles should be anticipated.
Publisher: Elsevier BV
Date: 11-2018
Location: China
Location: Italy
No related grants have been discovered for Francesco CUCCA.