Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data

BACKGROUND AND OBJECTIVES: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. METHODS: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. RESULTS: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an extended reference interval that takes into account the differences in platelet count observed in different geographic areas. CONCLUSIONS: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy

Variation of hemoglobin levels in normal Italian populations from genetic isolates.

Normal hemoglobin levels vary greatly according to genetic and acquired factors. As a consequence there is no general agreement on the definition of anemia in terms of hemoglobin levels. Here we compare the hemoglobin levels of subjects recruited from normal genetically isolated Italian populations whose medical history, life style habits and results of laboratory tests are available. After the exclusion of pathological samples we analyzed the hemoglobin levels of 3,849 subjects (1,661 males and 2,188 females) and evaluated the hemoglobin heritability. Normal subjects of different age groups from a northern Italian isolate have significantly higher hemoglobin levels when compared to matched subjects of southern Italian isolates. The estimated heritability of hemoglobin levels ranges from 0.34 to 0.42 in the different isolates. Our study provides a dataset of hemoglobin levels for normal subjects of different geographical origin and indicate that hemoglobin levels are substantially influenced by heritable components

New susceptibility locus for hypertension on chromosome 8q by efficient pedigree-breaking in an Italian isolate

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Whole Exome Sequencing Study of Parkinson Disease and Related Endophenotypes in the Italian Population

Parkinson Disease (PD) is a complex neurodegenerative disorder characterized by large genetic heterogeneity and missing heritability. Since the genetic background of PD can partly vary among ethnicities and neurological scales have been scarcely investigated in a PD setting, we performed an exploratory Whole Exome Sequencing (WES) analysis of 123 PD patients from mainland Italy, investigating scales assessing motor (UPDRS), cognitive (MoCA), and other non-motor symptoms (NMS). We performed variant prioritization, followed by targeted association testing of prioritized variants in 446 PD cases and 211 controls. Then we ran Exome-Wide Association Scans (EWAS) within sequenced PD cases (N = 113), testing both motor and non-motor PD endophenotypes, as well as their associations with Polygenic Risk Scores (PRS) influencing brain subcortical volumes. We identified a variant associated with PD, rs201330591 in GTF2H2 (5q13; alternative T allele: OR [CI] = 8.16[1.08; 61.52], FDR = 0.048), which was not replicated in an independent cohort of European ancestry (1,148 PD cases, 503 controls). In the EWAS, polygenic analyses revealed statistically significant multivariable associations of amygdala- [\u3b2(SE) = -0.039(0.013); FDR = 0.039] and caudate-PRS [0.043(0.013); 0.028] with motor symptoms. All subcortical PRSs in a multivariable model notably increased the variance explained in motor (adjusted-R2 = 38.6%), cognitive (32.2%) and other non-motor symptoms (28.9%), compared to baseline models (~20%). Although, the small sample size warrants further replications, these findings suggest shared genetic architecture between PD symptoms and subcortical structures, and provide interesting clues on PD genetic and neuroimaging features

Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss

Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium- and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both loci, we sought replication in two independent cohorts: B58C from the UK (N = 5892) and FITSA from Finland (N = 270). Both loci were successfully replicated at a nominal level of significance (P < 0.05). In order to confirm our quantitative findings, we carried out RT-PCR and reported RNA-Seq data, which showed that both genes are expressed in mouse inner ear, especially in hair cells, further suggesting them as good candidates for modulatory genes in the auditory system. Sequencing data revealed no functional variants in the coding region of PCDH20 or SLC28A3, suggesting that variation in regulatory sequences may affect expression. Overall, these results contribute to a better understanding of the complex mechanisms underlying human hearing function

To adapt or not to adapt: The question of domain-general cognitive control

a b s t r a c t What do perceptually bistable figures, sentences vulnerable to misinterpretation and the Stroop task have in common? Although seemingly disparate, they all contain elements of conflict or ambiguity. Consequently, in order to monitor a fluctuating percept, reinterpret sentence meaning, or say &apos;&apos;blue&apos;&apos; when the word RED is printed in blue ink, individuals must regulate attention and engage cognitive control. According to the Conflict Monitoring Theor

Heritability and Demographic Analyses in the Large Isolated Population of Val Borbera Suggest Advantages in Mapping Complex Traits Genes

Isolated populations are a useful resource for mapping complex traits due to shared stable environment, reduced genetic complexity and extended Linkage Disequilibrium (LD) compared to the general population. Here we describe a large genetic isolate from the North West Apennines, the mountain range that runs through Italy from the North West Alps to the South.The study involved 1,803 people living in 7 villages of the upper Borbera Valley. For this large population cohort, data from genealogy reconstruction, medical questionnaires, blood, anthropometric and bone status QUS parameters were evaluated. Demographic and epidemiological analyses indicated a substantial genetic component contributing to each trait variation as well as overlapping genetic determinants and family clustering for some traits.The data provide evidence for significant heritability of medical relevant traits that will be important in mapping quantitative traits. We suggest that this population isolate is suitable to identify rare variants associated with complex phenotypes that may be difficult to study in larger but more heterogeneous populations

Migraine attacks the Basal Ganglia

<p>Abstract</p> <p>Background</p> <p>With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month). The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human) brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF) to a matched (gender, age, age of onset and type of medication) group of patients whose migraine episodes progressed (HF).</p> <p>Results</p> <p>In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain.</p> <p>Conclusions</p> <p>Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.</p