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959 Publications visible to you, out of a total of 959
Association, characterisation and meta-analysis of SNPs linked to general reading ability in a German dyslexia case-control cohort
Genetical Statistics and Systems Biology

Abstract (Expand)

Dyslexia is a severe disorder in the acquisition of reading and writing. Several studies investigated the role of genetics for reading, writing and spelling ability in the general population. However, … many of the identified SNPs were not analysed in case-control cohorts. Here, we investigated SNPs previously linked to reading or spelling ability in the general population in a German case-control cohort. Furthermore, we characterised these SNPs for functional relevance with in silico methods and meta-analysed them with previous studies. A total of 16 SNPs within five genes were included. The total number of risk alleles was higher in cases than in controls. Three SNPs were nominally associated with dyslexia: rs7765678 within DCDC2, and rs2038137 and rs6935076 within KIAA0319. The relevance of rs2038137 and rs6935076 was further supported by the meta-analysis. Functional profiling included analysis of tissue-specific expression, annotations for regulatory elements and effects on gene expression levels (eQTLs). Thereby, we found molecular mechanistical implications for 13 of all 16 included SNPs. SNPs associated in our cohort showed stronger gene-specific eQTL effects than non-associated SNPs. In summary, our results validate SNPs previously linked to reading and spelling in the general population in dyslexics and provide insights into their putative molecular pathomechanisms.

Authors: Bent Müller, Arndt Wilcke, Ivonne Czepezauer, Peter Ahnert, Johannes Boltze, Holger Kirsten

Date Published: 1st Sep 2016

Publication Type: Journal article

Sleep disturbances and upregulation of brain arousal during daytime in depressed versus non-depressed elderly subjects.
LIFE Adult

Abstract (Expand)

OBJECTIVES: Although patients with depression often suffer from sleep disturbances, most of them are not sleepy. Upregulation of brain arousal has been proposed as pathophysiological mechanism explaining … sleep disturbances, inner tension, autonomic hyperarousal and anhedonia in depression. The aim of the current study was to examine the association between night-time sleep disturbances and brain arousal regulation the next day in depressed versus non-depressed subjects. METHODS: Twenty-eight elderly subjects (21 female; age = 70.5 +/- 4.4 years) with depressive syndromes without psychotropic medication, and 28 controls (22 female; age = 70.9 +/- 4.5 years), underwent a 15-min resting electroencephalogram; the Vigilance Algorithm Leipzig (VIGALL 2.1) provided an objective measure of brain arousal regulation. Sleep disturbances were assessed by a validated and self-rated sleep questionnaire. RESULTS: In the depressive group, but not in controls, more sleep disturbances were associated with a higher brain arousal stability score (high score corresponds to upregulation) the next day (sleep onset latency: rs = 0.69, P < .0001; sleep quality: rs = -0.59, P < .001). CONCLUSIONS: The data confirm the hypothesis that in persons with depressive syndromes sleep disturbances are related to upregulation of brain arousal the next day. This finding is in line with the concept that dysregulation of brain arousal is a central pathophysiological aspect in depression.

Authors: C. Ulke, C. Sander, P. Jawinski, N. Mauche, J. Huang, J. Spada, D. Wittekind, R. Mergl, T. Luck, S. Riedel-Heller, T. Hensch, U. Hegerl

Date Published: 25th Aug 2016

Publication Type: Journal article

Human Diseases: mental depression

FTO Obesity Risk Variants Are Linked to Adipocyte IRX3 Expression and BMI of Children - Relevance of FTO Variants to Defend Body Weight in Lean Children?
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene …e loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. AIM We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. RESULTS Expression of IRX3 was higher in adipocytes compared to SVF. We found increased adipocyte-specific expression of IRX3 and IRX5 with the presence of the FTO risk haplotype in lean children, whereas it was unaffected by risk variants in obese peers. We further show that IRX3 expression was elevated in isolated adipocytes and AT of lean compared to obese children, particularly in UCP1-negative adipocytes, and inversely correlated with BMI SDS. Independent of BMI, IRX3 expression in adipocytes was significantly related to adipocyte hypertrophy, and subsequent associations with AT inflammation and HOMA-IR in the children. CONCLUSION One interpretation of our observation of FTO risk variants linked to IRX3 expression and adipocyte size restricted to lean children, along with the decreased IRX3 expression in obese compared to lean peers, may reflect a defense mechanism for protecting body-weight, which is pertinent for lean children.

Authors: Kathrin Landgraf, Markus Scholz, Peter Kovacs, Wieland Kiess, Antje Körner

Date Published: 25th Aug 2016

Publication Type: Journal article

Comparing Measures of Association in 2x2 Probability Tables
Genetical Statistics and Systems Biology

Abstract

Not specified

Authors: Dirk Hasenclever, Markus Scholz

Date Published: 23rd Aug 2016

Publication Type: Journal article

Age-dependency of cardiac morphology and function: results of the LIFE-Adult-Study – analysis of the echocardiographic substudy
LIFE Adult

Abstract (Expand)

In the NORRE study (EHJCVI (2014) 15, 680 – 690) normal values determined by echocardiography were published in healthy subjects (n = 734) with mean age of 46+13 years (range: 20 – 78). Left ventricular … (LV)-volumes showed good correlations to the participants' (pts') age. LV-volumes were decreased and LV ejection fraction (EF) was increased according to the increase of the pts' age. A significant correlation between age and LV-mass was only found in women. Left atrial (LA)-volumes did not significantly change with age. Parameters of diastolic function showed a strong age-dependency (decrease of E/A-ratio; increase of E/E'-ratio). In the present LIFE-Adult analysis echocardiographic parameters were compared to the NORRE data. In 773 pts (326 males and 447 females; median age: 51 years), standardised transthoracic echocardiography was performed according to the national and international recommendations. The following parameters were analysed: LV- and LA-volume analyses by M-Mode measurements and 2D-LV planimetry, maximum E-and A-velocity, E/A-ratio and E/E'-ratio. The cohort was divided in age related subcohorts between 20 – 40, 41 – 50 and 51 – 60 years. Mean LV-diameter was 54 ± 5 mm (males) and 49 ± 4 mm (females). There was no age-dependency in males, but a tendency of LV-diameter increase in females. Mean LA diameter was 39 ± 4 mm in males and 35 ± 4 mm in females. Mean LA-diameter-index was 20 ± 2 mm/m2 (males) and 20 ± 3 mm/m2 (females) showing Age-dependency of an increasing LA-diameter in males and females. LV mass-index was 100 ± 20 g/m2 (males) and 83 ± 19 g/m2 (females) showing a tendency of increasing LV mass-index with age in males and females. Subsequently, septal and posterior wall thickness slightly increases with age. No differences of LVEF with increase of the pts' age could be observed. E/A-ratio was decreased and E/E'-ratio was increased with increase of the pts' age. The analysis of the echocardiographic parameters of the LIFE-Adult trial showed differences of the age-dependency in comparison to the NORRE data.

Authors: S. Stöbe, A. Hagendorff, S. Zeynalova, S. Tautenhahn, K. Wirkner, G. Farese, D. Jurisch, D. Pfeiffer, M. Loeffler

Date Published: 18th Aug 2016

Publication Type: Journal article

Correlation of the E/E'-ratio to NT-BNP: echocardiographic subanalysis of the LIFE-Adult-Study
LIFE Adult

Abstract (Expand)

The E/E'-ratio is used as a surrogate parameter for the estimation of the left ventricular enddiastolic pressure. It is assumed that chronic systolic and diastolic heart failure is associated with … E/E'-values of more than 15 or at least with intermediate values between 9 – 5. The aim of the present retrospective analysis of the epidemiological echocardiographic cohort of the LIFE-Adult study (Leipzig Research Centre for Civilization Diseases) was to evaluate the correlation of NT-BNP (N-terminales propeptid BNP) values to the E/E'-ratio by the assessment of left ventricular diastolic function in this cohort. In 773 participants (pts) standardised transthoracic echocardiography was performed and in 748 pts NT-BNP was analysed. The E/E'-ratio was determined according to the international recommendations by measuring the maximum velocity of the early diastolic inflow by pulsed wave Doppler echocardiography and the basal septal maximum myocardial velocity by tissue Doppler echocardiography at early diastole. NT-BNP was determined using commercially available diagnostic tests. Pathological NT-BNP levels were assumed in the range > 222pg/ml. Normal E/E'-ratios as well as normal NT-BNP levels were observed in 91% of all participants. In 1.4% of the pts elevated NT-BNP levels were found in the presence of normal E/E'-ratio. In contrast in 1.1% of the pts elevated E/E'-ratios were found in the presence of normal NT-BNP levels. Most of the pts with heart failure detected by NT-BNP vales > 222pg/ml also showed intermediate E/E'-ratios between 9 and 15 (42pts). In only 0.8% of the pts (5 pts) significantly elevated E/E'-ratios > 15 and pathological NT-BNP levels could be observed (see fig). Only 4 pts with elevated NT-BNP values showed left ventricular systolic dysfunction. E/E'-ratio has to be verified to be suitable for the detection of heart failure patients. The present data show that E/E'-ratio of > 15 is not well correlated to increased NT-BNP levels.

Authors: S. Stöbe, A. Hagendorff, S. Zeynalova, S. Tautenhahn, S. Wirkner, F. Gerardo, D. Jurisch, D. Pfeiffer, M. Loeffler

Date Published: 18th Aug 2016

Publication Type: Journal article

Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia.
LIFE Adult

Abstract (Expand)

Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, … particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the posterior BF, and most severe in the semantic variant and the nonfluent variant of PPA. Structural covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p < .001, permutation test). In contrast, the PPA patients showed preserved structural covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p < .001, permutation test). Our findings agree with the neuroanatomically proposed involvement of the cholinergic BF, particularly the NSP, in PPA syndromes. We found a shift from a structural covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA.

Authors: S. Teipel, T. Raiser, L. Riedl, I. Riederer, M. L. Schroeter, S. Bisenius, A. Schneider, J. Kornhuber, K. Fliessbach, A. Spottke, M. J. Grothe, J. Prudlo, J. Kassubek, A. Ludolph, B. Landwehrmeyer, S. Straub, M. Otto, A. Danek

Date Published: 11th Aug 2016

Publication Type: Journal article

Human Diseases: aphasia

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