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251 Publications visible to you, out of a total of 251
Prevalence of atrial fibrillation dependent on coronary artery status: Insights from the LIFE-Heart Study.
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: Coronary artery disease (CAD) is a significant risk factor for atrial fibrillation (AF). Experimental studies demonstrated that atrial ischemia induced by right coronary artery (RCA) stenosis … promote AF triggers and development of electro-anatomical substrate for AF. AIM: To analyze the association between AF prevalence and coronary arteries status in the LIFE-Heart Study. METHODS: This analysis included patients with available coronary catheterization data recruited between 2006 and 2014. Patients with acute myocardial infarction were excluded. CAD was defined as stenosis >/=75%, while coronary artery sclerosis (CAS) was defined as non-critical plaque(s) <75%. RESULTS: In total, 3.458 patients (median age 63 years, 34% women) were included into analysis. AF was diagnosed in 238 (6.7%) patients. There were 681 (19.7%) patients with CAS and 1.411 (40.8%) with CAD (27.5% with single, 32.4% with double, and 40.1% with triple vessel CAD). In multivariable analysis, there was a significant association between prevalent AF and coronary artery status (OR 0.64, 95% CI 0.53-0.78, Ptrend < .001). Similarly, AF risk was lower in patients with higher CAD extent (OR 0.54, 95%CI 0.35-0.83, Ptrend = .005). Compared to single vessel CAD, the risk of AF was lower in double (OR 0.42, 95%CI 0.19-0.95, P = .037) and triple CAD (OR 0.31, 95%CI 0.13-0.71, P = .006). Finally, no association was found between AF prevalence and CAD origin among patients with single vessel CAD. CONCLUSION: In the LIFE-Heart Study, CAS but not CAD was associated with increased risk of AF.

Authors: J. Kornej, S. Henger, T. Seewoster, A. Teren, R. Burkhardt, H. Thiele, J. Thiery, M. Scholz

Date Published: 27th Oct 2020

Publication Type: Journal article

Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study.
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: Obesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, … such as reward processing. Yet, few studies have investigated the association of obesity, related genetic variants, and structural connectivity of the dopaminergic reward network. METHODS: We analyzed 347 participants (age range: 20-59 years, BMI range: 17-38 kg/m(2)) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a microarray. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 T using deterministic tractography of Freesurfer-derived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions. We used linear models to test the association of BMI, risk alleles of both variants, and reward network connectivity. RESULTS: Higher BMI was significantly associated with lower connectivity strength for number of streamlines (beta = -0.0025, 95%-C.I.: [-0.004, -0.0008], p = 0.0042), and, to lesser degree, fractional anisotropy (beta = -0.0009, 95%-C.I. [-0.0016, -0.00008], p = 0.031), but not clustering coefficient. Strongest associations were found for left putamen, right accumbens, and right lateral orbitofrontal cortex. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F = 6.9, p < 0.001). None of the genetic variants was associated with reward network structural connectivity. CONCLUSIONS: Here, we provide evidence that higher BMI correlates with lower reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not observe an association of variants in FTO or near DRD2 receptor with reward network structural connectivity in this population-based cohort with a wide range of BMI and age. Future research should further investigate the link between genetics, obesity and fronto-striatal structural connectivity.

Authors: F. Beyer, R. Zhang, M. Scholz, K. Wirkner, M. Loeffler, M. Stumvoll, A. Villringer, A. V. Witte

Date Published: 25th Oct 2020

Publication Type: Journal article

Neurobiological origins of individual differences in mathematical ability.
Genetical Statistics and Systems Biology

Abstract (Expand)

Mathematical ability is heritable and related to several genes expressing proteins in the brain. It is unknown, however, which intermediate neural phenotypes could explain how these genes relate to … mathematical ability. Here, we examined genetic effects on cerebral cortical volume of 3-6-year-old children without mathematical training to predict mathematical ability in school at 7-9 years of age. To this end, we followed an exploration sample (n = 101) and an independent replication sample (n = 77). We found that ROBO1, a gene known to regulate prenatal growth of cerebral cortical layers, is associated with the volume of the right parietal cortex, a key region for quantity representation. Individual volume differences in this region predicted up to a fifth of the behavioral variance in mathematical ability. Our findings indicate that a fundamental genetic component of the quantity processing system is rooted in the early development of the parietal cortex.

Authors: M. A. Skeide, K. Wehrmann, Z. Emami, H. Kirsten, A. M. Hartmann, D. Rujescu

Date Published: 22nd Oct 2020

Publication Type: Journal article

The Obesity-Susceptibility Gene TMEM18 Promotes Adipogenesis through Activation of PPARG.
Genetical Statistics and Systems Biology

Abstract (Expand)

TMEM18 is the strongest candidate for childhood obesity identified from GWASs, yet as for most GWAS-derived obesity-susceptibility genes, the functional mechanism remains elusive. We here investigate … the relevance of TMEM18 for adipose tissue development and obesity. We demonstrate that adipocyte TMEM18 expression is downregulated in children with obesity. Functionally, downregulation of TMEM18 impairs adipocyte formation in zebrafish and in human preadipocytes, indicating that TMEM18 is important for adipocyte differentiation in vivo and in vitro. On the molecular level, TMEM18 activates PPARG, particularly upregulating PPARG1 promoter activity, and this activation is repressed by inflammatory stimuli. The relationship between TMEM18 and PPARG1 is also evident in adipocytes of children and is clinically associated with obesity and adipocyte hypertrophy, inflammation, and insulin resistance. Our findings indicate a role of TMEM18 as an upstream regulator of PPARG signaling driving healthy adipogenesis, which is dysregulated with adipose tissue dysfunction and obesity.

Authors: K. Landgraf, N. Kloting, M. Gericke, N. Maixner, E. Guiu-Jurado, M. Scholz, A. V. Witte, F. Beyer, J. T. Schwartze, M. Lacher, A. Villringer, P. Kovacs, A. Rudich, M. Bluher, W. Kiess, A. Korner

Date Published: 20th Oct 2020

Publication Type: Journal article

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.
Genetical Statistics and Systems Biology

Abstract (Expand)

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are … warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 x 10(-6)) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 x 10(-13)), bipolar disorder (1.53[1.44; 1.63]; p = 1 x 10(-43)), schizophrenia (1.36[1.28; 1.45]; p = 4 x 10(-22)), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 x 10(-12)), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 x 10(-4)), educational attainment (0.86[0.82; 0.91]; p = 2 x 10(-7)), and intelligence (0.72[0.68; 0.76]; p = 9 x 10(-29)). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

Authors: A. Gialluisi, T. F. M. Andlauer, N. Mirza-Schreiber, K. Moll, J. Becker, P. Hoffmann, K. U. Ludwig, D. Czamara, B. S. Pourcain, F. Honbolygo, D. Toth, V. Csepe, G. Huguet, Y. Chaix, S. Iannuzzi, J. F. Demonet, A. P. Morris, J. Hulslander, E. G. Willcutt, J. C. DeFries, R. K. Olson, S. D. Smith, B. F. Pennington, A. Vaessen, U. Maurer, H. Lyytinen, M. Peyrard-Janvid, P. H. T. Leppanen, D. Brandeis, M. Bonte, J. F. Stein, J. B. Talcott, F. Fauchereau, A. Wilcke, H. Kirsten, B. Muller, C. Francks, T. Bourgeron, A. P. Monaco, F. Ramus, K. Landerl, J. Kere, T. S. Scerri, S. Paracchini, S. E. Fisher, J. Schumacher, M. M. Nothen, B. Muller-Myhsok, G. Schulte-Korne

Date Published: 14th Oct 2020

Publication Type: Journal article

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
Genetical Statistics and Systems Biology

Abstract (Expand)

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely … unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

Authors: S. Vogelezang, J. P. Bradfield, T. S. Ahluwalia, J. A. Curtin, T. A. Lakka, N. Grarup, M. Scholz, P. J. van der Most, C. Monnereau, E. Stergiakouli, A. Heiskala, M. Horikoshi, I. O. Fedko, N. Vilor-Tejedor, D. L. Cousminer, M. Standl, C. A. Wang, J. Viikari, F. Geller, C. Iniguez, N. Pitkanen, A. Chesi, J. Bacelis, L. Yengo, M. Torrent, I. Ntalla, O. Helgeland, S. Selzam, J. M. Vonk, M. H. Zafarmand, B. Heude, I. S. Farooqi, A. Alyass, R. N. Beaumont, C. T. Have, P. Rzehak, J. R. Bilbao, T. M. Schnurr, I. Barroso, K. Bonnelykke, L. J. Beilin, L. Carstensen, M. A. Charles, B. Chawes, K. Clement, R. Closa-Monasterolo, A. Custovic, J. G. Eriksson, J. Escribano, M. Groen-Blokhuis, V. Grote, D. Gruszfeld, H. Hakonarson, T. Hansen, A. T. Hattersley, M. Hollensted, J. J. Hottenga, E. Hypponen, S. Johansson, R. Joro, M. Kahonen, V. Karhunen, W. Kiess, B. A. Knight, B. Koletzko, A. Kuhnapfel, K. Landgraf, J. P. Langhendries, T. Lehtimaki, J. T. Leinonen, A. Li, V. Lindi, E. Lowry, M. Bustamante, C. Medina-Gomez, M. Melbye, K. F. Michaelsen, C. S. Morgen, T. A. Mori, T. R. H. Nielsen, H. Niinikoski, A. J. Oldehinkel, K. Pahkala, K. Panoutsopoulou, O. Pedersen, C. E. Pennell, C. Power, S. A. Reijneveld, F. Rivadeneira, A. Simpson, P. D. Sly, J. Stokholm, K. K. Teo, E. Thiering, N. J. Timpson, A. G. Uitterlinden, C. E. M. van Beijsterveldt, B. D. C. van Schaik, M. Vaudel, E. Verduci, R. K. Vinding, M. Vogel, E. Zeggini, S. Sebert, M. V. Lind, C. D. Brown, L. Santa-Marina, E. Reischl, C. Frithioff-Bojsoe, D. Meyre, E. Wheeler, K. Ong, E. A. Nohr, T. G. M. Vrijkotte, G. H. Koppelman, R. Plomin, P. R. Njolstad, G. D. Dedoussis, P. Froguel, T. I. A. Sorensen, B. Jacobsson, R. M. Freathy, B. S. Zemel, O. Raitakari, M. Vrijheid, B. Feenstra, L. P. Lyytikainen, H. Snieder, H. Kirsten, P. G. Holt, J. Heinrich, E. Widen, J. Sunyer, D. I. Boomsma, M. R. Jarvelin, A. Korner, G. Davey Smith, J. C. Holm, M. Atalay, C. Murray, H. Bisgaard, M. I. McCarthy, V. W. V. Jaddoe, S. F. A. Grant, J. F. Felix

Date Published: 13th Oct 2020

Publication Type: Journal article

Transcriptomic Research in Heart Failure with Preserved Ejection Fraction: Current State and Future Perspectives.
Genetical Statistics and Systems Biology

Abstract (Expand)

Heart failure with preserved ejection fraction (HFpEF) is increasing in incidence and has a higher prevalence compared with heart failure with reduced ejection fraction. So far, no effective treatment … of HFpEF is available, due to its complex underlying pathophysiology and clinical heterogeneity. This article aims to provide an overview and a future perspective of transcriptomic biomarker research in HFpEF. Detailed characterisation of the HFpEF phenotype and its underlying molecular pathomechanisms may open new perspectives regarding early diagnosis, improved prognostication, new therapeutic targets and tailored therapies accounting for patient heterogeneity, which may improve quality of life. A combination of cross-sectional and longitudinal study designs with sufficiently large sample sizes are required to support this concept.

Authors: S. Rosch, K. P. Rommel, M. Scholz, H. Thiele, P. Lurz

Date Published: 12th Oct 2020

Publication Type: Journal article

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