Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Digitaaliongelma. Kirjoitus oikeudesta ja ympäristöstä

Tutkielma vanhoista sääntöjärjestelmistä uudessa digitaalisessa ympäristössä. Teos laajentaa oikeudellisia kysymyksiä kultuurisiin, taloudellisiin ja yhteisöllisiin taustoihin selventäen sekä menneisyyttä että tulevaisuuden haasteita ja monikansallista sääntörjäestelmää. Teos on osoitettu etenkin opiskelijoille mutta se osallistuu lisäksi meneillään olevaan keskusteluun informaation sääntelynkeinoista.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Litteraturvetenskap

Samlingen med signum HB IVa finns vid huvudbiblioteket och innehåller litteraturvetenskaplig litteratur till och med år 1999. Litteraturvetenskaplig litteratur finns dessutom vid Humanistiska biblioteket i anslutning till ämnet Litteraturvetenskap. Litteraturvetenskaplig litteratur har ingått i talrika donationer till akademibiblioteket. Som exempel på donatorer kan nämnas J.V.Brummer, Eva Kihlman, Axel Söderholm, Ella Grönberg, Ragnar Numelin, Harry Streng, Karin Allardt Ekelund, Carin Rosenius, Thora Gripenberg, Signe Mattsson, Johannes Åkesson, Sigurd von Pfaler, Karin Spoof. Friexemplaren som erhållits från 1919 samt inköp har kompletterat samlingen. Återvinning av litteraturvetenskaplig litteratur tryckt före 1980 görs genom manuell sökning i huvudbibliotekets systematiska kortkatalog. Retroaktiv inmatning i databasen Alma gör att litteratur tryckt mellan 1830 och 1979 med tiden blir sökbart i Alma med sökfunktionen Signum och söktermen HB IVa. Från och med år 2000 ingår den litteraturvetenskapliga litteraturen vid huvudbiblioteket i en numerus currens-samling.

Carnap and Kuhn on linguistic frameworks and scientific revolutions

Several recent works in history and philosophy of science have re-evaluated the alleged opposition between the theses put forth by logical empiricists such as Carnap and the so-called "post-positivists", such as Kuhn. Although the latter came to be viewed as having seriously challenged the logical positivist views of science, recent authors (e.g., Friedman, Reisch, Earman, Irzik and Grünberg) maintain that some of the most notable theses of the Kuhnian view of science have striking similarities with some aspects of Carnap's philosophy. Against that reading, Oliveira and Psillos argue that within Carnap's philosophy there is no place for the Kuhnian theses of incommensurability, holism, and theory-ladenness of observations. This paper presents each of those readings and argues that Carnap and Kuhn have non-opposing views on holism, incommensurability, the theory-ladenness of observations, and scientific revolutions. We note at the very end - without dwelling on the point, however - that they come apart on other matters, such as their views on metaphysics and on the context of discovery/justification distinction.

Aimo-hiilikaasutin

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Atlas hinnasto N:o 11

kuv., 10 x 15 cm

Atlas hinnasto N:o 11

kuv., 10 x 15 cm

Luettelo sisältäen mitat ja hinnat mäntärenkaita mäntiä mäntätappeja venttiilejä

kuv., 21 x 18 cm

Luettelo "Sim" tuotteista

kuv., 22 x 18 cm

Mäntiä, mäntärenkaita, mäntätappeja, venttiilejä

kuv., 22 x 17 cm

Kahdenkymmenenkahden, 22, solmun nopeus!

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Amal kaasuttajien hoito-ohjeet ja varaosa-luettelo

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Miten kaksi patentoitua yksityiskohtaa tekevät "Gates" tuulettajan hihnat vahvemmiksi ja kulumista kestävämmiksi

kuv., 22 x 27 cm