A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Pitkittäisaineistojen analyysista latenttien muuttujien malleilla

Summary: Analyzing longitudinal data using latent-variable models

Suomi-promootiota yhteistyössä : Kansalliskirjasto ja UM

kysymykset Esko Rahikainen

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.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

Osaaminen tietämyksen tukena kehitettäessä aikuisopiston työprosesseja

Osaaminen voi muodostua ongelmaksi yritysten kilpailukyvylle, jos siihen ei kiinnitetä huomiota jo strategiasuunnittelusta lähtien. Vaikka asiakkaiden muuttuneet odotukset kyettäisiinkin kohdentamaan ennen kilpailijoita, saattaa olla, että siihen ei pystytä vastaamaan, jos ei ehditä oppimaan uutta tai uudella tavalla. Diplomityön tavoitteena on laatia Etelä-Karjalan aikuisopistollehenkilöstön osaamisen kehittämiskuvaus siitä, kuinka strategian määrittämisestälähtien voidaan henkilöstön osaamista parantaa ja pyrkiä luomaan kilpailuetua markkinoilla. Henkilöstön osaamisen kehittäminen tulee olla suunnitelmallista, tarvittaessa yksilön, ryhmän ja organisaation edut huomioivaa, riittävän yksinkertaista ja konkreettista, jotta suunnitelma voidaan toteuttaa, seurata ja edelleenkehittää. Työn teoriaosassa on kuvattu vision ja strategian merkitystä osaamisen kehittämiseen. Lisäksi on tarkasteltu yksilön oppimista, oppimisen prosessia ja sen kehittymistä organisaation kyvykkyydeksi. Osaamisen infrastruktuuria on lähestytty organisaatiokulttuurin, sitouttamisen ja kehittämisjärjestelmän näkökulmasta. Empiirisessä osuudessa on tuotu esiin aikuisopiston henkilöstön osaamisen kehittämisen tavoitteet, nykyiset käytännöt, kehittämisen vaihtoehdot sekä jatkotoimenpiteet. Osaaminen on aikuisopiston henkilöstön ammattitaidon perusta. Osaamistarpeen määrittämisen tulee keskittyä aikuisopiston ydinosaamisen kehittämiseen. Henkilöstö tulisi nähdä motivoinnin ja sitouttamisen kautta inhimillistä tietopääomaa kasvattavana tekijänä, johon voidaan sujuvasti liittää aineeton pääoma (data, informaatio jne.) sekä strateginen reservi, kuten kilpailuetua tuottava innovointitoiminta.