| 1. |
- Furberg, Helena, et al.
(författare)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 2. |
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| 3. |
- Schumacher, J, et al.
(författare)
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Linkage analyses of chromosomal region 18p11-q12 in dyslexia
- 2006
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Ingår i: Journal of neural transmission. - Vienna, Austria : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 113:3, s. 417-23
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Tidskriftsartikel (refereegranskat)abstract
- Dyslexia is characterized as a significant impairment in reading and spelling ability that cannot be explained by low intelligence, low school attendance or deficits in sensory acuity. It is known to be a hereditary disorder that affects about 5% of school aged children, making it the most common of childhood learning disorders. Several susceptibility loci have been reported on chromosomes 1, 2, 3, 6, 15, and 18. The locus on chromosome 18 has been described as having the strongest influence on single word reading, phoneme awareness, and orthographic coding in the largest genome wide linkage study published to date (Fisher et al., 2002). Here we present data from 82 German families in order to investigate linkage of various dyslexia-related traits to the previously described region on chromosome 18p11-q12. Using two- and multipoint analyses, we did not find support for linkage of spelling, single word reading, phoneme awareness, orthographic coding and rapid naming to any of the 14 genotyped STR markers. Possible explanations for our non-replication include differences in study design, limited power of our study and overestimation of the effect of the chromosome 18 locus in the original study.
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| 4. |
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| 5. |
- Preis, S, et al.
(författare)
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Munich atopy prediction study (MAPS): protocol for a prospective birth cohort addressing clinical and molecular risk factors for atopic dermatitis in early childhood
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e059256-
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of atopic diseases is highly complex, and the exact mechanisms leading to atopic dermatitis (AD) onset in infants remain mostly enigmatic. In addition to an interdependent network of components of skin development in young age and skin barrier dysfunction underlying AD development that is only partially understood, a complex interplay between environmental factors and lifestyle habits with skin barrier and immune dysregulation is suspected to contribute to AD onset. This study aims to comprehensively evaluate individual microbiome and immune responses in the context of environmental determinants related the risk of developing AD in the first 4 years of a child’s life.Methods and analysesThe ‘Munich Atopic Prediction Study’ is a comprehensive clinical and biological investigation of a prospective birth cohort from Munich, Germany. Information on pregnancy, child development, environmental factors, parental exposures to potential allergens and acute or chronic diseases of children and parents are collected by questionnaires together with a meticulous clinical examination by trained dermatologists focusing on allergies, skin health, and in particular signs of AD at 2 months after birth and then every 6 months. In addition, skin barrier functions are assessed through cutometry, corneometry and transepidermal water loss at every visit. These measurements are completed with allergy diagnostics and extensive microbiome analyses from stool and skin swabs as well as transcriptome analyses using skin microbiopsies.The aim is to assess the relevance of different known and yet unknown risk factors of AD onset and exacerbations in infants and to identify possible accessible and robust biomarkers.Ethics and disseminationThe study is approved by the Ethical Committee of the Medical Faculty of the Technical University of Munich (reference 334/16S). All relevant study results will be presented at national and international conferences and in peer-reviewed journals.
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| 6. |
- Schumann, Gunter, et al.
(författare)
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KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
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Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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| 7. |
- Brant, Luisa C. C., et al.
(författare)
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Association Between Electrocardiographic Age and Cardiovascular Events in Community Settings : The Framingham Heart Study
- 2023
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Ingår i: Circulation. Cardiovascular Quality and Outcomes. - : Ovid Technologies (Wolters Kluwer Health). - 1941-7713 .- 1941-7705. ; 16:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Deep neural networks have been used to estimate age from ECGs, the electrocardiographic age (ECG-age), which predicts adverse outcomes. However, this prediction ability has been restricted to clinical settings or relatively short periods. We hypothesized that ECG-age is associated with death and cardiovascular outcomes in the long-standing community-based FHS (Framingham Heart Study).METHODS: We tested the association of ECG-age with chronological age in the FHS cohorts in ECGs from 1986 to 2021. We calculated the gap between chronological and ECG-age (& UDelta;age) and classified individuals as having normal, accelerated, or decelerated aging, if & UDelta;age was within, higher, or lower than the mean absolute error of the model, respectively. We assessed the associations of & UDelta;age, accelerated and decelerated aging with death or cardiovascular outcomes (atrial fibrillation, myocardial infarction, and heart failure) using Cox proportional hazards models adjusted for age, sex, and clinical factors.RESULTS:The study population included 9877 FHS participants (mean age, 55 & PLUSMN;13 years; 54.9% women) with 34 948 ECGs. ECG-age was correlated to chronological age (r=0.81; mean absolute error, 9 & PLUSMN;7 years). After 17 & PLUSMN;8 years of follow-up, every 10-year increase of & UDelta;age was associated with 18% increase in all-cause mortality (hazard ratio [HR], 1.18 [95% CI, 1.12-1.23]), 23% increase in atrial fibrillation risk (HR, 1.23 [95% CI, 1.17-1.29]), 14% increase in myocardial infarction risk (HR, 1.14 [95% CI, 1.05-1.23]), and 40% increase in heart failure risk (HR, 1.40 [95% CI, 1.30-1.52]), in multivariable models. In addition, accelerated aging was associated with a 28% increase in all-cause mortality (HR, 1.28 [95% CI, 1.14-1.45]), whereas decelerated aging was associated with a 16% decrease (HR, 0.84 [95% CI, 0.74-0.95]).CONCLUSIONS:ECG-age was highly correlated with chronological age in FHS. The difference between ECG-age and chronological age was associated with death, myocardial infarction, atrial fibrillation, and heart failure. Given the wide availability and low cost of ECG, ECG-age could be a scalable biomarker of cardiovascular risk.
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| 8. |
- Knaapila, Matti, et al.
(författare)
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An effect of side chain length on the solution structure of poly(9,9-dialkylfluorene)s in toluene
- 2008
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Ingår i: Polymer. - : Elsevier BV. - 0032-3861. ; 49:8, s. 2033-2038
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Tidskriftsartikel (refereegranskat)abstract
- The effect of side chain length of pi-conjugated poly(9,9-dialkylfluorene)s has been studied in semi-dilute (10 mg/mL) toluene solutions using small-angle neutron scattering (SANS) and H-1 and H-2 NMR spectroscopies. Under these conditions, SANS data indicate that poly(9,9-dinonylfluorene) and poly(9,9-dioctylfluorene) are dissolved down to the molecule level and appear as elongated one-dimensional chains (length >20-30 nm). In contrast, the shorter side chain polymers exhibit a self-association so that poly(9,9-diheptylfluorene) forms thin sheet-like (similar to 1 nm) and poly(9,9-dihexylfluorene) thin (similar to 1 nm) and thick sheet-like (>6 nm) aggregates. H-1 NMR data, together with the density functional theory (DFT) calculations, however, show that this occurs without changes in the conformation of the polymer backbone.
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| 9. |
- Knaapila, Matti, et al.
(författare)
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Control over phase behavior and solution structure of hairy-rod polyfluorene by means of side-chain length and branching
- 2008
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Ingår i: Physical Review E (Statistical, Nonlinear, and Soft Matter Physics). - 1539-3755. ; 77:5
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Tidskriftsartikel (refereegranskat)abstract
- We present guidelines on how the solution structure of pi-conjugated hairy-rod polyfluorenes is controlled by the side-chain length and branching. First, the semiquantitative mean-field theory is formulated to predict the phase behavior of the system as a function of side-chain beads (N). The phase transition at N=N* separates a lyotropic phase with solvent coexistence (N < N*) and a metastable membrane phase (N > N*). The membrane phase transforms into the isotropic phase of dissolved rodlike polymers at the temperature T-mem*(N), which decreases both with N and with the degree of side-chain branching. This picture is complemented by polymer demixing with the transition temperature T-IN*(N), which decreases with N. For N < N*, the lyotropic phase turns isotropic with increasing T at T-IN*. For N > N*, stable membranes are predicted for T-IN*< T < T-mem* and metastable membranes with nematic coexistence for T < T-IN*. Second, in experiment, samples of poly(9,9-dialkylfluorene) with N=6-10 were mixed in methylcyclohexane. For N=8 the side-chain branching was controlled by (9,9-dioctylfluorene)/(9,9-bis(2-ethylhexyl)fluorene) (F8/F2/6) random copolymers. The proportion of F8 to F2/6 repeat units was 100:0, 95:5, 90:10, 50:50, and 0:100. In accordance with the theory, lyotropic, membrane, and isotropic phases with the corresponding phase transitions were observed. For N < N*similar to 6 only the lyotropic phase is present for attainable temperatures. The membrane and isotropic phases are present for N > N*. T-mem*(N) decreases from 340 K to 280 K for N >= 8. For copolymers, the membrane phase is found when the fraction of F8 units is at least 90%, T-mem* decreasing with this fraction. The membrane phase contains three material types: loose sheets of two polymer layers, a better packed beta phase, and dissolved polymer. For N >= 7 and T < T-mem* the tendency for membrane formation becomes stronger with increasing temperature.
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| 10. |
- Knaapila, Matti, et al.
(författare)
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Influence of side chain length on the self-assembly of hairy-rod poly(9,9-dialkylfluorene)s in the poor solvent methylcyclohexane
- 2007
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Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 40:26, s. 9398-9405
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Tidskriftsartikel (refereegranskat)abstract
- We report on the phase behavior of poly(9,9-dihexylfluorene) (PF6), poly(9,9-diheptylfluorene) (PF7), poly(9,9-diocylfluorene) (PF8) poly(9,9-dinonylfluorene) (PF9), and poly(9,9-didecylfluorene) (PF10) in methylcyclohexane (MCH). After a heating-cooling cycle, in the 10-50 mg/mL. concentration range. PF6/ MCH. PF7/MCH. PF8/MCH, and PF9/MCH systems were found to be gel-like, while PF10/MCH appears less viscous. PF6/MCH, PF7/MCH, PF8/MCH, and PF9/MCH form large (10- 100 nm) sheetlike assemblies (thickness of 2-3 nm). The larger length scale Structures of these sheets show an odd-even dependence on the side chain (spacer) length: the PF6 and PF8 sheets are broader and thinner, whereas PF7 and PF9 sheets are thicker with a Putative double layer Structure. PF10 does not follow this sequence, and only part of the polymer is assembled into a sheetlike structure the rest remaining dissolved at the molecular level. PF8/MCH and PF9/MCH mixtures also have lower length scale crystalline structures with an internal period corresponding to the periodicity observed in the solid-state P phase of PF8. Vestiges of crystalline domains are found for PF6 and PF7 but not for PF10. PF7/MCH. PF8/MCH, and PF9/MCH systems contain the conformational isomer C, of those chains observed in the ss phase, while this is not observed with other polymer/MCH systems.
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