@phdthesis{Kubas2005, author = {Kubas, Daniel}, title = {Applications of Galactic Microlensing}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-5179}, school = {Universit{\"a}t Potsdam}, year = {2005}, abstract = {Subject of this work is the study of applications of the Galactic Microlensing effect, where the light of a distant star (source) is bend according to Einstein's theory of gravity by the gravitational field of intervening compact mass objects (lenses), creating multiple (however not resolvable) images of the source. Relative motion of source, observer and lens leads to a variation of deflection/magnification and thus to a time dependant observable brightness change (lightcurve), a so-called microlensing event, lasting weeks to months. The focus lies on the modeling of binary-lens events, which provide a unique tool to fully characterize the lens-source system and to detect extra-solar planets around the lens star. Making use of the ability of genetic algorithms to efficiently explore large and intricate parameter spaces in the quest for the global best solution, a modeling software (Tango) for binary lenses is developed, presented and applied to data sets from the PLANET microlensing campaign. For the event OGLE-2002-BLG-069 the 2nd ever lens mass measurement has been achieved, leading to a scenario, where a G5III Bulge giant at 9.4 kpc is lensed by an M-dwarf binary with total mass of M=0.51 solar masses at distance 2.9 kpc. Furthermore a method is presented to use the absence of planetary lightcurve signatures to constrain the abundance of extra-solar planets.}, subject = {Planeten}, language = {en} } @article{ClarkeLauchtRidingeretal.2011, author = {Clarke, Toni-Kim and Laucht, Manfred and Ridinger, Monika and Wodarz, Norbert and Rietschel, Marcella and Maier, Wolfgang and Lathrop, Mark and Lourdusamy, Anbarasu and Zimmermann, Ulrich S. and Desrivieres, Sylvane and Schumann, Gunter}, title = {KCNJ6 is associated with adult alcohol dependence and involved in gene x early life stress interactions in adolescent alcohol drinking}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {36}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, number = {6}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/npp.2010.247}, pages = {1142 -- 1148}, year = {2011}, abstract = {Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. One SNP, rs2836016, was found to be associated with alcohol dependence (p = 0.01, false discovery rate). We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene-environment interactions. In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p = 0.01). Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.}, language = {en} } @article{HuberLeziusReibisetal.2015, author = {Huber, Matthias and Lezius, Susanne and Reibis, Rona Katharina and Treszl, Andras and Kujawinska, Dorota and Jakob, Stefanie and Wegscheider, Karl and V{\"o}ller, Heinz and Kreutz, Reinhold}, title = {A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy}, series = {International journal of molecular sciences}, volume = {16}, journal = {International journal of molecular sciences}, number = {8}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms160817456}, pages = {17456 -- 17468}, year = {2015}, abstract = {Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 +/- 9.8 years, 83\% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) 40\% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7\%) and myocardial infarction (n = 545; 54.1\%) with a mean LVEF of 59.9\% +/- 9.3\%. The mean left ventricular mass index (LVMI) was 52.1 +/- 21.2 g/m(2.7) and 485 (48.2\%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7\% increase in LVMI (95\% CI: 1\%-12\%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.}, language = {en} } @article{AlgharablyBolbrinkerLeziusetal.2017, author = {Algharably, Engi A. H. and Bolbrinker, Juliane and Lezius, Susanne and Reibis, Rona Katharina and Wegscheider, Karl and V{\"o}ller, Heinz and Kreutz, Reinhold}, title = {Uromodulin associates with cardiorenal function in patients with hypertension and cardiovascular disease}, series = {Journal of hypertension}, volume = {35}, journal = {Journal of hypertension}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0263-6352}, doi = {10.1097/HJH.0000000000001432}, pages = {2053 -- 2058}, year = {2017}, abstract = {Objective:Common genetic variants in the gene encoding uromodulin (UMOD) have been associated with renal function, blood pressure (BP) and hypertension. We investigated the associations between an important single nucleotide polymorphism (SNP) in UMOD, that is rs12917707-G>T, and estimated glomerular filtration rate (eGFR), BP and cardiac organ damage as determined by echocardiography in patients with arterial hypertension.Methods:A cohort of 1218 treated high-risk patients (mean age 58.5 years, 83\% men) with documented cardiovascular disease (81\% with coronary heart disease) was analysed.Results:The mean values for 24-h SBP and DBP were 124.714.7 and 73.9 +/- 9.4mmHg; mean eGFR was 77.5 +/- 18.3ml/min per 1.73m(2), mean left ventricular ejection fraction was 59.3 +/- 9.9\% and mean left ventricular mass index in men and women was 53.9 +/- 23.2 and 54.9 +/- 23.7g/m(2.7) with 50.4\% of patients having left ventricular hypertrophy. A significant association between rs12917707 and eGFR was observed with T-allele carriers showing significantly higher eGFR values (+2.6ml/min per 1.73m(2), P=0.006) than noncarriers. This SNP associated also with left atrial diameter (P=0.007); homozygous carriers of the T-allele had smaller left atrial diameter (-1.5mm) than other genotype groups (P=0.040). No significant associations between rs12917707 and other cardiac or BP phenotypes were observed.Conclusions:These findings extend the previously documented role of UMOD for renal function also to treated high-risk patients with arterial hypertension and reveal a novel association with left atrial remodelling and thus a potential cardiorenal link modulated by UMOD.}, language = {en} } @misc{BeaumontWarringtonCavadinoetal.2017, author = {Beaumont, Robin N. and Warrington, Nicole M. and Cavadino, Alana and Tyrrell, Jessica and Nodzenski, Michael and Horikoshi, Momoko and Geller, Frank and Myhre, Ronny and Richmond, Rebecca C. and Paternoster, Lavinia and Bradfield, Jonathan P. and Kreiner-M{\o}ller, Eskil and Huikari, Ville and Metrustry, Sarah and Lunetta, Kathryn L. and Painter, Jodie N. and Hottenga, Jouke-Jan and Allard, Catherine and Barton, Sheila J. and Espinosa, Ana and Marsh, Julie A. and Potter, Catherine and Zhang, Ge and Ang, Wei and Berry, Diane J. and Bouchard, Luigi and Das, Shikta and Hakonarson, Hakon and Heikkinen, Jani and Helgeland, {\O}yvind and Hocher, Berthold and Hofman, Albert and Inskip, Hazel M. and Jones, Samuel E. and Kogevinas, Manolis and Lind, Penelope A. and Marullo, Letizia and Medland, Sarah E. and Murray, Anna and Murray, Jeffrey C. and Nj{\o}lstad, Pa ̊l R. and Nohr, Ellen A. and Reichetzeder, Christoph and Ring, Susan M. and Ruth, Katherine S. and Santa-Marina, Loreto and Scholtens, Denise M. and Sebert, Sylvain and Sengpiel, Verena and Tuke, Marcus A. and Vaudel, Marc and Weedon, Michael N. and Willemsen, Gonneke and Wood, Andrew R. and Yaghootkar, Hanieh and Muglia, Louis J. and Bartels, Meike and Relton, Caroline L. and Pennell, Craig E. and Chatzi, Leda and Estivill, Xavier and Holloway, John W. and Boomsma, Dorret I. and Montgomery, Grant W. and Murabito, Joanne M. and Spector, Tim D. and Power, Christine and Ja ̈rvelin, Marjo-Ritta and Bisgaard, Hans and Grant, Struan F.A. and S{\o}rensen, Thorkild I.A. and Jaddoe, Vincent W. and Jacobsson, Bo and Melbye, Mads and McCarthy, Mark I. and Hattersley, Andrew T. and Hayes, M. Geoffrey and Frayling, Timothy M. and Hivert, Marie-France and Felix, Janine F. and Hyppo ̈nen, Elina and Lowe, William L. , Jr and Evans, David M. and Lawlor, Debbie A. and Feenstra, Bjarke and Freathy, Rachel M.}, title = {Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {628}, issn = {1866-8372}, doi = {10.25932/publishup-42310}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-423100}, pages = {15}, year = {2017}, abstract = {Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 {\^A} 10 {\`A}8 . In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.}, language = {en} } @misc{TianReichetzederLietal.2019, author = {Tian, Mei and Reichetzeder, Christoph and Li, Jian and Hocher, Berthold}, title = {Low birth weight, a risk factor for diseases in later life, is a surrogate of insulin resistance at birth}, series = {Journal of hypertension}, volume = {37}, journal = {Journal of hypertension}, number = {11}, publisher = {Kluwer}, address = {Philadelphia}, issn = {0263-6352}, doi = {10.1097/HJH.0000000000002156}, pages = {2123 -- 2134}, year = {2019}, abstract = {Low birth weight (LBW) is associated with diseases in adulthood. The birthweight attributed risk is independent of confounding such as gestational age, sex of the newborn but also social factors. The birthweight attributed risk for diseases in later life holds for the whole spectrum of birthweight. This raises the question what pathophysiological principle is actually behind the association. In this review, we provide evidence that LBW is a surrogate of insulin resistance. Insulin resistance has been identified as a key factor leading to type 2 diabetes, cardiovascular disease as well as kidney diseases. We first provide evidence linking LBW to insulin resistance during intrauterine life. This might be caused by both genetic (genetic variations of genes controlling glucose homeostasis) and/or environmental factors (due to alterations of macronutrition and micronutrition of the mother during pregnancy, but also effects of paternal nutrition prior to conception) leading via epigenetic modifications to early life insulin resistance and alterations of intrauterine growth, as insulin is a growth factor in early life. LBW is rather a surrogate of insulin resistance in early life - either due to inborn genetic or environmental reasons - rather than a player on its own.}, language = {en} } @article{FriebelHermanussenScheffler2019, author = {Friebel, Francis and Hermanussen, Michael and Scheffler, Christiane}, title = {Popular ideas and convictions about factors influencing the growth as well as the adult height of children}, series = {Journal of biological and clinical anthropology : Anthropologischer Anzeiger ; Mitteilungsorgan der Gesellschaft f{\"u}r Anthropologie}, volume = {76}, journal = {Journal of biological and clinical anthropology : Anthropologischer Anzeiger ; Mitteilungsorgan der Gesellschaft f{\"u}r Anthropologie}, number = {5}, publisher = {Schweizerbart}, address = {Stuttgart}, issn = {0003-5548}, doi = {10.1127/anthranz/2019/0972}, pages = {365 -- 370}, year = {2019}, abstract = {Common knowledge suggests that growth in height is influenced by nutrition, genetics, health, and environmental and general living conditions. In addition, modern studies showed that also social mobility and dominance within the social group, may significantly affect adolescent growth and final height. The aim of the study was to investigate the impact of popular ideas and beliefs about factors influencing the growth on the biology of child and adolescent growth. We hypothesized that these beliefs are culture-specific and age-dependent. We investigated 307 French and 315 German participants of all age-groups. We collected polarising statements by questionnaire that the participants had to agree or disagree on. French participants see a connection between nutrition and the body height of children. This is different in Germany and may be due to the fact that French food culture is more traditional. Genetic factors were generally overestimated and considered as the most important determinants of longitudinal-growth. The participants denied an influence of disease and social status. Participants over 35 years of age considered adult height to be independent of environmental factors. In conclusion, popular beliefs partly depend on culture and appear to change with age as a result of growing experience.}, language = {en} } @misc{HuberLeziusReibisetal., author = {Huber, Matthias and Lezius, Susanne and Reibis, Rona Katharina and Treszl, Andras and Kujawinska, Dorota and Jakob, Stefanie and Wegscheider, Karl and V{\"o}ller, Heinz and Kreutz, Reinhold}, title = {A single nucleotide polymorphism near the CYP17A1 gene is associated with left ventricular mass in hypertensive patients under pharmacotherapy}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400074}, pages = {13}, abstract = {Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83\% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥40\% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7\%) and myocardial infarction (n = 545; 54.1\%) with a mean LVEF of 59.9\% ± 9.3\%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2\%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7\% increase in LVMI (95\% CI: 1\%-12\%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.}, language = {en} }