Stefania Bandinelli

Azienda Sanitaria di Firenze, Florens, Tuscany, Italy

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Publications (270)1840.14 Total impact

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    ABSTRACT: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). We conducted meta-analyses (N to 11668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein) and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma vs. erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary ALA and linoleic acid for DHA and DPA. Our findings reinforce earlier reports that genetically-based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Molecular Nutrition & Food Research 01/2015; · 4.91 Impact Factor
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    ABSTRACT: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake. Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile. Trials related to this study were registered at clinicaltrials.gov as NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT01331512 [Invecchiare in Chianti (Aging in the Chianti Area) study], NCT00289237 (Inter99), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis). © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 01/2015; 101(1):135-43. · 6.50 Impact Factor
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    ABSTRACT: Background It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease.ResultsWe performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P¿=¿0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person¿s risk of death by 1.57%.Conclusions This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.
    BMC Genetics 12/2014; 15(1):1274. · 2.36 Impact Factor
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    ABSTRACT: Faster resting heart rate (HR), which is associated with inflammation and elevated cortisol levels, is a risk factor for excess cardiovascular morbidity and mortality. Obesity is associated with increased cardiovascular morbidity and mortality, inflammation, and elevated cortisol levels. The aim of the present study was to evaluate the interaction of Body Mass Index (BMI) with inflammation and cortisol in modulating HR in older subjects. We analyzed data of 895 participants aged 65+ enrolled in the "InCHIANTI" study, in sinus rhythm, and not taking beta blockers or digoxin. Linear regression was performed to assess the adjusted association between HR, IL-6, and cortisol levels. The model was also analyzed stratifying for BMI tertiles. Logistic regression was adopted for evaluating the association of HR exceeding the mean value with Il-6 and serum cortisol. According to multivariable linear regression, IL-6 and cortisol levels were associated with HR (B = 1.42, 95% CI = 0.43-2.42; p = .005 and B = .34, 95% CI = 0.17-.51; p < .0001, respectively). The association was significant only among women in the highest BMI tertile (B = 4.16, 95% CI = 1.40-6.91; p = .003 for IL-6 and B = .57, 95% CI = 0.14-1.01; p = .010 for cortisol). Logistic regression confirmed that IL-6 and cortisol levels were associated with HR above the mean value in the highest BMI tertile (OR = 2.13, 95% CI = 1.15-3.97; p = .009 and OR = 1.14, 95% CI = 1.03-1.25; p = .009, respectively). Faster HR is associated with proinflammatory state in elderly patients; this association seems to be limited to women with higher BMI. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 11/2014; · 4.31 Impact Factor
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    ABSTRACT: Initial results from sequencing studies suggest that there are relatively few low frequency (<5%) variants associated with large effects on common phenotypes. We performed low pass whole genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: i) that sequencing would detect single low frequency - large effect variants that explained similar amounts of phenotypic variance as single common variants, and ii) that some common variant associations could be explained by low frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant - common phenotype associations - 11,132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11,657,229 high quality variants of which 6,129,221 and 5,528,008 were common and low frequency (<5%) respectively, low frequency - large effect associations comprised 7% of detectable cis-gene expression traits (89 of 1,314 cis-eQTLs at P<1x10(-06) (FDR ∼5%)) and 1 of 8 biomarker associations at P<8x10(-10). Very few (30 of 1,232; 2%) common variant associations were fully explained by low frequency variants. Our data show that whole genome sequencing can identify low frequency variants undetected by genotyping based approaches when sample sizes are sufficiently large to detect substantial numbers of common variant associations, and that common variant associations are rarely explained by single low frequency variants of large effect.
    Human Molecular Genetics 11/2014; 24(5). · 6.68 Impact Factor
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    ABSTRACT: Current operational definitions of sarcopenia are based on algorithms' simultaneous considering measures of skeletal muscle mass and muscle-specific as well as global function. We hypothesize that quantitative and qualitative sarcopenia-related parameters may not be equally predictive of incident disability, thus presenting different clinical relevance.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 10/2014; · 4.31 Impact Factor
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    ABSTRACT: Objectives To develop and test a postal screening questionnaire to intercept frailty in older community-dwelling individuals.DesignA questionnaire was developed on the basis of expert consensus and preliminarily tested against the occurrence of incident disability, in secondary analyses of previous epidemiological studies. The questionnaire was then mailed and its concurrent validity, defined from the association between its individual items and summary score and the presence of the Fried frailty phenotype (FFP), was subsequently evaluated cross-sectionally with in-person examination of initial participants.SettingCommunity-based.ParticipantsIndividuals aged 70 and older living in two communities near Florence, Italy.MeasurementsA home comprehensive geriatric assessment including the FFP was conducted in participants who screened positive for frailty and in a limited sample of negative responders.ResultsA 10-item questionnaire, developed based on expert consensus, was preliminarily tested on preexisting epidemiological data and showed an area under the receiver operating characteristic curve (AUC) of 0.716 versus incident disability. The questionnaire was then mailed to 15,774 subjects, whose response rate was 53.6%. Of the first 1,037 participants included in the concurrent validation study, 833 (80.3%) screened positive, and 380 (36.6%) were frail on assessment. The ability of the questionnaire summary score to predict frailty was adequate, with an AUC of 0.695, a sensitivity of 71%, and a specificity of 58%.ConclusionA simple questionnaire delivered by mail was able to identify FFP in the community. This would facilitate large-scale screening for frailty in older persons.
    Journal of the American Geriatrics Society 10/2014; · 4.22 Impact Factor
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    ABSTRACT: Arising from G. Hemani et al. 508, 249-253 (2014); doi:10.1038/nature13005Epistasis occurs when the effect of a genetic variant on a trait is dependent on genotypes of other variants elsewhere in the genome. Hemani et al. recently reported the detection and replication of many instances of epistasis between pairs of variants influencing gene expression levels in humans. Using whole-genome sequencing data from 450 individuals we strongly replicated many of the reported interactions but, in each case, a single third variant captured by our sequencing data could explain all of the apparent epistasis. Our results provide an alternative explanation for the apparent epistasis observed for gene expression in humans. There is a Reply to this Brief Communication Arising by Hemani, G. et al. Nature 514, http://dx.doi.org/10.1038/nature13692 (2014).
    Nature 10/2014; 514(7520):E3-5. · 42.35 Impact Factor
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    ABSTRACT: The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2014; · 4.31 Impact Factor
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    ABSTRACT: Multimorbidity increases with aging, but risk factors beyond age are unknown.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2014; · 4.31 Impact Factor
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    ABSTRACT: White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior GWAS meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50,000 individuals from three diverse populations (Japanese, African-American, and European-ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil, and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine map the putatively causal variants within loci. Lastly, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis, and 9 secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.
    Human Molecular Genetics 08/2014; · 6.68 Impact Factor
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    ABSTRACT: In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1-adjusted for age, sex, and parathyroid hormone (PTH); model 2-including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (β ± SE = -0.11 ± 0.03, p = <0.0001) and log (hsCRP) (β ± SE = -0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (β ± SE = -0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (β ± SE = -0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.
    European geriatric medicine 08/2014; 36(4):9694. · 0.55 Impact Factor
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    ABSTRACT: Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight exposure warrant investigation. The purpose of this study was to assess the effects of sunlight exposure on CD4+ T-cell methylation patterns on an epigenome-wide scale in a North American population of European origin (n = 991). In addition, we investigated the genetic contribution to epigenetic variation (methylQTL). We used linear regression to test the associations between methylation scores at 461 281 cytosine-phosphate-guanine (CpG) sites and sunlight exposure, followed by a genome-wide association analysis (methylQTL) to test for associations between methylation at the top CpG locus and common genetic variants, assuming an additive genetic model. We observed an epigenome-wide significant association between sunlight exposure and methylation status at cg26930596 (p = 9.2 × 10−8), a CpG site located in protein kinase C zeta (PRKCZ), a gene previously shown to be entrained by light. MethylQTL analysis resulted in significant associations between cg26930596 and two intergenic single nucleotide polymorphisms on chromosome 3, rs4574216 (p = 1.5 × 10−10) and rs4405858 (p = 1.9 × 10−9). These common genetic variants reside downstream of WWTR1, a transcriptional co-activator of PRKCZ. Associations observed in the North American population, however, did not replicate in an independent Mediterranean cohort. Our preliminary results support the role of sunlight exposure in epigenetic processes, and lay the groundwork for future studies of the molecular link between sunlight and physiologic processes such as tumorigenesis and metabolism.
    Chronobiology International 07/2014; · 2.88 Impact Factor
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    ABSTRACT: Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97—0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96—0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87—0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
    The Lancet Diabetes and Endocrinology. 06/2014;
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    ABSTRACT: Although metabolic syndrome (MS) is a typical condition of middle-aged/older person, the association between MS and mortality risk has not been confirmed in people over 65 years. We hypothesized that while in the elderly MS phenotype might lose its value in predicting mortality risk, the two core factors of MS, i.e. insulin resistance (IR) and low grade systemic inflammation (LGSI) would not.
    Atherosclerosis 06/2014; 235(2):538-545. · 3.71 Impact Factor
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    ABSTRACT: IMPORTANCE Resveratrol, a polyphenol found in grapes, red wine, chocolate, and certain berries and roots, is considered to have antioxidant, anti-inflammatory, and anticancer effects in humans and is related to longevity in some lower organisms. OBJECTIVE To determine whether resveratrol levels achieved with diet are associated with inflammation, cancer, cardiovascular disease, and mortality in humans. DESIGN Prospective cohort study, the Invecchiare in Chianti (InCHIANTI) Study ("Aging in the Chianti Region"), 1998 to 2009 conducted in 2 villages in the Chianti area in a population-based sample of 783 community-dwelling men and women 65 years or older. EXPOSURES Twenty-four-hour urinary resveratrol metabolites. MAIN OUTCOMES AND MEASURES Primary outcome measure was all-cause mortality. Secondary outcomes were markers of inflammation (serum C-reactive protein [CRP], interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]) and prevalent and incident cancer and cardiovascular disease. RESULTS Mean (95% CI) log total urinary resveratrol metabolite concentrations were 7.08 (6.69-7.48) nmol/g of creatinine. During 9 years of follow-up, 268 (34.3%) of the participants died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of participants who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P = .67). Participants in the lowest quartile had a hazards ratio for mortality of 0.80 (95% CI, 0.54-1.17) compared with those in the highest quartile of total urinary resveratrol in a multivariable Cox proportional hazards model that adjusted for potential confounders. Resveratrol levels were not significantly associated with serum CRP, IL-6, IL-1β, TNF, prevalent or incident cardiovascular disease, or cancer. CONCLUSIONS AND RELEVANCE In older community-dwelling adults, total urinary resveratrol metabolite concentration was not associated with inflammatory markers, cardiovascular disease, or cancer or predictive of all-cause mortality. Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study.
    JAMA Internal Medicine 05/2014; 174(7). · 13.25 Impact Factor
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    ABSTRACT: Background Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies. Methods Data were from 851 participants (65-94 years) of the InCHIANTI Study and 1,064 (26-93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up. Results In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p = 0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p = 0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference. Conclusions The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications.
    Psychoneuroendocrinology 04/2014; · 5.59 Impact Factor
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    ABSTRACT: Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2×10-8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.
    PLoS ONE 01/2014; 9(12):e111156. · 3.53 Impact Factor
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    Journal of the American Geriatrics Society 01/2014; 62(1). · 4.22 Impact Factor
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    ABSTRACT: Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.
    Nature Communications 01/2014; 5:4926. · 10.74 Impact Factor

Publication Stats

10k Citations
1,840.14 Total Impact Points

Institutions

  • 2006–2014
    • Azienda Sanitaria di Firenze
      Florens, Tuscany, Italy
    • Università degli Studi di Palermo
      Palermo, Sicily, Italy
    • University of Florida
      • Department of Aging and Geriatric Research
      Gainesville, FL, United States
  • 2013
    • University of Turku
      • Department of Public Health
      Turku, Province of Western Finland, Finland
    • Queen's University
      • School of Rehabilitation Therapy
      Kingston, Ontario, Canada
  • 2012–2013
    • Harvard Medical School
      Boston, Massachusetts, United States
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2011–2013
    • LIUCBM Libera Università Campus Bio-Medico di Roma
      • Endocrinology and Diabetes Unit
      Roma, Latium, Italy
    • University of Barcelona
      • Department of Physiology
      Barcelona, Catalonia, Spain
    • Medizinische Universität Innsbruck
      • Sektion für Genetische Epidemiologie
      Innsbruck, Tyrol, Austria
    • National Institute for Health and Welfare, Finland
      • Department of Health, Functional Capacity and Welfare
      Helsinki, Province of Southern Finland, Finland
    • University of Delaware
      • Department of Physical Therapy
      Newark, DE, United States
  • 2008–2013
    • Universita degli studi di Ferrara
      • • Section of Internal Medicine, Gerontology and Geriatrics
      • • Department of Morphology, Surgery and Experimental Medicine
      Ferrare, Emilia-Romagna, Italy
    • University Hospital of Parma
      Parma, Emilia-Romagna, Italy
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      Chieta, Abruzzo, Italy
  • 2005–2013
    • University of Florence
      • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      Florens, Tuscany, Italy
    • Catholic University of the Sacred Heart
      • School of Geriatrics
      Roma, Latium, Italy
    • Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana
      Roma, Latium, Italy
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
    • Northwestern University
      • Department of Medicine
      Evanston, IL, United States
  • 2010–2012
    • University of Exeter
      • • Peninsula College of Medicine and Dentistry
      • • Department of Biosciences
      Exeter, ENG, United Kingdom
    • University of Michigan
      • Department of Biostatistics
      Ann Arbor, MI, United States
  • 2008–2012
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, MD, United States
  • 2004–2011
    • Università degli studi di Parma
      • Department of Clinical and Experimental Medicine
      Parma, Emilia-Romagna, Italy
    • Wake Forest School of Medicine
      • Sticht Center on Aging
      Winston-Salem, NC, United States
  • 2003–2011
    • National Institute on Aging
      • • Laboratory of Epidemiology, Demography and Biometry (LEDB)
      • • Clinical Research Branch (CRB)
      Baltimore, MD, United States
  • 2009
    • Università degli Studi di Perugia
      • Department of Clinical and Experimental Medicine
      Perugia, Umbria, Italy
    • MedStar Health Research Institute
      Maryland, United States
    • Case Western Reserve University
      Cleveland, Ohio, United States
    • University of Southern California
      Los Angeles, California, United States
    • Second University of Naples
      Caserta, Campania, Italy
    • Kansas City VA Medical Center
      Kansas City, Missouri, United States
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2006–2009
    • Fondazione Don Carlo Gnocchi
      Milano, Lombardy, Italy
  • 2005–2009
    • National Institutes of Health
      • • Laboratory of Epidemiology, Demography, and Biometry (LEDB)
      • • Clinical Research Branch (CRB)
      Bethesda, MD, United States
  • 2007
    • University of Washington Seattle
      • Department of Rehabilitation Medicine
      Seattle, WA, United States
  • 1999–2006
    • INRCA Istituto Nazionale di Ricovero e Cura per Anziani
      Ancona, The Marches, Italy
  • 2003–2005
    • University of Naples Federico II
      Napoli, Campania, Italy