Assessment of gene-by-sex interaction effect on bone mineral density

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.Medtronic NIH R01 AG18728 R01HL088119 R01AR046838 U01 HL084756 R01 AR43351 P01-HL45522 R01-MH-078111 R01-MH-083824 Nutrition and Obesity Research Center of Maryland P30DK072488 NIAMS/NIH F32AR059469 Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034 PI08/0183 Canadian Institutes of Health Research (CIHR) NHLBI HHSN268201200036C N01-HC-85239 N01-HC-85079 N01-HC-85086 N01-HC-35129 N01 HC15103 N01 HC-55222 N01-HC-75150 N01-HC-45133 HL080295 HL087652 HL105756 NIA AG-023629 AG-15928 AG-20098 AG-027058 N01AG62101 N01AG62103 N01AG62106 1R01AG032098-01A1 National Center of Advancing Translational Technologies CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Diseases DK063491 EUROSPAN (European Special Populations Research Network) European Commission FP6 STRP grant 018947 LSHG-CT-2006-01947 Netherlands Organisation for Scientific Research Erasmus MC Centre for Medical Systems Biology (CMSB) Netherlands Brain Foundation (HersenStichting Nederland) US National Institute for Arthritis, Musculoskeletal and Skin Diseases National Institute on Aging R01 AR/AG41398 R01 AR050066 R21 AR056405 National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc. N02-HL-6-4278 Canadian Institutes of Health Research from Institute of Aging 165446 Institute of Genetics 179433 Institute of Musculoskeletal health 221765 Intramural Research Program of the NIH, National Institute on Aging National Institutes of Health HHSN268200782096C Hong Kong Research Grant Council HKU 768610M Bone Health Fund of HKU Foundation KC Wong Education Foundation Small Project Funding 201007176237 Matching Grant CRCG Grant Osteoporosis and Endocrine Research Fund Genomics Strategic Research Theme of The University of Hong Kong Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Erasmus Medical Center and Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam German Bundesministerium fur Forschung und Technology 01 AK 803 A-H 01 IG 07015

Materialien fuer Lithium-Ionen-Batterien mit fluessigen organischen Elektrolyten Abschlussbericht

Die derzeit kommerziell erhaeltlichen Li-Ion Zellen beinhalten LiCoO_2 als Kathodenmaterial und LiPF_6 als Leitsalz. Ziel des Projekts war Ersatz des teuren LiCoO_2 durch billige Mn-Spinelle Li_1_+_xMn_2O_4 und Entwicklung neuer Elektrolyte und Leitsalze. Realisiert wurde dies durch den Verbund von industriellen Partnern (Merck, VARTA) und Spezialisten aus der Forschung. Das Projekt konnte in den wesentlichen zwei Punkten zum Erfolg gefuehrt werden. Erstens durch die Erarbeitung einer kostenguenstigen Spinellsynthese, die erfolgreich in die Pilotproduktion ueberfuehrt werden konnte. Zweitens durch die Erarbeitung von Aufreinigungs- und Trocknungsmethoden fuer Li-Ion taugliche Loesungsmittel und die Ueberfuehrung dieser Methoden in den industriellen Massstab. Mit den neuen Materialien wurde ein Feldtest mit 50 Wickelzellen der Baugroesse AA durchgefuehrt. Die Testergebnisse zeigen, dass Zellen mit Li-Methid Elektrolyt gegenueber Standardzellen mit LiPF_6 Elektrolyt bei vergleichbaren elektrochemischen Daten ein verbessertes Sicherheitsverhalten zeigen. (orig.)In the commercial Lithium Ion Batteries LiCoO_2 as cathode and LiPF_6 as conductive salt is used. The objectives of the project were to replace the expensive LiCoO_2 by lithium manganese spinel Li_1_+_xMn_2O_4 and the development of new salts and electrolytes. This work was realized by the close cooperation of industrial partners and researchers from the university. Both objectives was accomplished successfully. It was elaborated a simple and cheap synthesis route for Li_1_+_xMn_2O_4 which was successfully scaled-up. Different methods of purification and drying to battery grade solvents were established and scaled up. With the new materials fifty AA-sized batteries were built and tested. The results showed that cells which contain Li-Methid conducting salt showed better safety characteristics as cells with LiPF_6-based electrolytes. (orig.)SIGLEAvailable from TIB Hannover: F99B739+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

A critical comparison of typologies of small-scale forestry in Baden-Württemberg derived using single and multiple criteria

The paper presents a typology of small-scale forest owners in Baden-Württemberg based on multiple criteria and derived using multivariate cluster analysis of long-term accountancy network data. Four distinct types of landholders are identified based on a combination of structural, financial and biophysical data. These groups fit well with the present knowledge on small-scale forest owners in Baden-Württemberg. In addition, the members of each group display clear differences in attitudes towards forestry, giving further support for the validity of the grouping. A comparison is made of this typology and typologies derived using the single criteria of forestry region, forest size class, cutting volume, proportion of coniferous trees, forest income and main source of income. This comparison demonstrates the advantages of using cluster analysis to identify types of small-scale forest owners in south-west Germany. No matter whether structural, natural or financial data are assessed, the multiple criteria typology produced by cluster analysis provides the highest percentage of statistically significant distinctions between the medians of the groups identified. A typology based on the single criterion of ‘regions’ provides the second best fit and has the advantage of being simple to develop. A more detailed comparison between these two typologies, whereby the differences between groups were analysed based on the links between individual groups in respect to individual variables, also indicated that the multiple criteria typology was superior