Towards a translational medical research ecosystem

In this paper we introduce a novel design for a translational medical research ecosystem. Translational medical research is an emerging field of work, which aims to bridge the gap between basic medical science research and clinical research/patient care. We analyze the key challenges of digital ecosystems for translational research, based on real world scenarios posed by the Lab for Translational Research at the Harvard Medical School and the Genomics Research Centre of the Griffith University, and show how traditional IT approaches fail to fulfill these challenges. We then introduce our design for a translational research ecosystem. Several key contributions are made: A novel approach to managing ad-hoc research ecosystems is introduced; a new security approach for translational research is proposed which allows each participating site to retain control over its data and define its own policies to ensure legal and ethical compliance; and a design for a novel interactive access control framework which allows users to easily share data, while adhering to their organization's policies is presented.

How can partnerships between the universities and schools exploit new opportunities for pedagogies at the intersection of the arts/design and the sciences?

Driven by information accessibility-on-demand provided by the internet, education modes are changing from a teacher-led approach focused on content delivery and assessible outcomes, to a learner-based approach encouraging self-directed, peer-tutored, and cooperative learning. New pedagogies are required to extend learning beyond the classroom and traditional subject areas such as contemporary arts, in alignment with the cross disciplinary priorities of the Australian Curriculum and values of the International Baccalaureate Organisation. This research explores how partnerships with universities and cultural organisations are implicated in the generation of these new forms of pedagogy and contribute to the field of educational research within the context of Education Queensland’s Framework For Gifted Education. In particular, this paper explores a new pedagogical framework for highly capable year five to nine Queensland state school students at the intersection of arts, design and the sciences, which has arisen from an explicit secondary/ tertiary partnership between the Queensland University of Technology Creative Industries Faculty and Precincts and the Queensland Academies Young Scholars Program. The Young Scholars Program offers experiences in the International Baccalaureate and Australian Curriculum contexts to enhance outcomes via global understanding, unique industry partnerships and 21st century pedagogical innovation based not on 'content' but tacit/experiential learning concepts including immersive, creative, intellectual and social strategies. These strategies for highly capable students are centred around authentic opportunities, primary resources, transdisciplinary learning and relationships with likeminded peers including tertiary arts, design and STEM educators and students, professionals and researchers. The presentation details case studies which are hands-on real time workshops involving inquiry based challenges in the arts, design and sciences, mathematics, history, creative writing and other disciplines, with content drawn from collections from public institutions, academic research and tertiary pedagogy. Both programs implicate student collaboration and creative production as methodology/data capture for ongoing action research, in alignment with the Framework For Gifted Education’s emphasis on evidence-based practices. They also challenge gifted students “to continue their development through curricular activities that require depth of study, complexity of thinking, fast pace of learning, high-level skills development and/or creative and critical thinking (e.g. through independent investigations, tiered tasks, diverse real-world applications, mentors)”(Education Queensland, 2011:3). This presentation highlights the strengths of the ongoing collaboration between QUT Creative industries Faculty and Queensland Academies, which not only provides successful extra curricular activities for gifted students towards a place in the International Baccalaureate Program, but also provides mentoring opportunities for tertiary students in their field of endeavor to assist with their own learning, and unique research opportunities for the Faculty as it focuses on excellence in arts, design and creative education and research. Education Queensland.(2011). Framework For Gifted Education Revised Edition 2011 (accessed Nov 19 2011)

100 futures now : designing sustainable futures

This presentation tells the story of an initiative in middle schooling at Kelvin Grove State College that begins in the Art studios, but reaches out to other disciplines and approaches, and to community and industry partners. It is inspired by the potential of 'future thinking' to become a compelling focus in contemporary art and design. Ethically it espouses a simple premise": every student in our classrooms now has a stake in creating livable, democratic and creative futures. Every student has the potential to be an active force in making that future. "100 Futures Now" is a project that envisages creative and imaginative students working in collaboration with artists and designers to visualize amazing futures and communicate their vision through art and design. "100 Futures Now" is one in a series of innovative curriculum initiatives at Kelvin Grove State College designed to build sustainable practice in arts education with the support of partners in industry and universities and with resident artists and designers. The model blends elements of art and design methodology to focus on the critical and creative thinking skills prioritised in ACARA and 21st century curriculum. The organisers are developing a sustainable model for working with resident artists that goes beyond a single arts intervention or extension/enrichment experience. In this model artists and designers are collaborators in the design of learning experiences that support future programs. This model also looks to transfer the benefits of residencies to the wider school community (in this case to middle schooling curriculum) and to teachers in other curriculum areas, and not exclusively to the immediate target group. In "100 Futures Now", story-making is the engine that powers the creative process. For this reason the program uses a series of imaginative scenarios, including those of speculative fiction and science, as departure points for inquiry, and applies the methodologies of arts and design practice to explore and express student story telling and story making. The story-making responses of student teams will naturally be expressed multimodally through visual art, design artifacts, installation, performance and digital works. The project’s focus on narratives and its modes of communication (performance/installation) are inspired by the work of experimental contemporary design practices and the speculative scenarios of U.K. based designers Anthony Dunne and Fiona Raby. Thanks to the support of an Arts Queensland Artist-in -Residence grant in 2014, resident artists and designers who work with a diversity of ideas and approaches ranging over science, bio-ethics, biodiversity, behavior and ethics, ambient sound, urbanism, food, and wearable design, will work with middle school students as catalysts for deeper thinking and creative action. All these rich fields for future speculation will become triggers for team inquiry into the deeper connections between the past, the present, and future challenges such as climate, waste, energy, sustainability and resilience. These imagined futures will form the platform for a critical, sustainability/design futures approach that will involve questioning assumptions and empowering students as agents rather than consumers of change.

Talking across the fence : partners for art education

This presentation explores a model for building and sustaining secondary – tertiary partnerships in Arts education. It traces the evolution of partner relationships in a challenging educational landscape, assesses the value of dialogue between educators, design professionals and community stakeholders, and tells the story of a particular secondary – tertiary partnership exploring new pedagogy in Art and Design, between Kelvin Grove State College, the School of Design Creative Industries Faculty of QUT, and the Design Minds program of the State Library of Queensland. Among other benefits, tertiary and industry partners have brought a myriad of diverse voices into the classrooms, enabled the direct interaction of learners with tertiary student mentors, and with art and design practitioners. The working model has also now matured into formal and informal partner agreements that help guarantee its viability into the future. This presentation, which deals with the opening of new terrain between committed partners, is also the story of how design has gradually been integrated in the curriculum, enriching and expanding the repertoire of Art programs, and how one Visual Art Faculty in a large inner city Brisbane School has adopted design thinking and “metadesign” as a model for future innovation. From the process of interaction and dialogue among educators and practitioners over several years has emerged a conviction that both partnering and design pedagogy are key tools in developing forward thinking curriculum for the Arts. In addition, hammering out a model that works for students across different year levels and in diverse settings by putting ideas into practice and micro-managing this process in studios and workshops has challenged teachers to rethink their own Art pedagogy. Finally, in the ecosystem of Schools and in the wider systems that are now driving change in education, survival for the Arts may depend on the networking and affirmation derived from innovating partners. Our story, the story of committed individuals who have sustained a dialogue across boundaries, may provide a valuable model for other arts educators fighting to retain agency in their schools.

Clinical and economic outcomes of nutrition interventions across the continuum of care

Optimal nutrition across the continuum of care plays a key role in the short- and long-term clinical and economic outcomes of patients. Worldwide, an estimated one-quarter to one-half of patients admitted to hospitals each year are malnourished. Malnutrition can increase healthcare costs by delaying patient recovery and rehabilitation and increasing the risk of medical complications. Nutrition interventions have the potential to provide cost-effective preventive care and treatment measures. However, limited data exist on the economics and impact evaluations of these interventions. In this report, nutrition and health system researchers, clinicians, economists, and policymakers discuss emerging global research on nutrition health economics, the role of nutrition interventions across the continuum of care, and how nutrition can affect healthcare costs in the context of hospital malnutrition.

ICEPOLE: High-speed, hardware-oriented authenticated encryption

This paper introduces our dedicated authenticated encryption scheme ICEPOLE. ICEPOLE is a high-speed hardware-oriented scheme, suitable for high-throughput network nodes or generally any environment where specialized hardware (such as FPGAs or ASICs) can be used to provide high data processing rates. ICEPOLE-128 (the primary ICEPOLE variant) is very fast. On the modern FPGA device Virtex 6, a basic iterative architecture of ICEPOLE reaches 41 Gbits/s, which is over 10 times faster than the equivalent implementation of AES-128-GCM. The throughput-to-area ratio is also substantially better when compared to AES-128-GCM. We have carefully examined the security of the algorithm through a range of cryptanalytic techniques and our findings indicate that ICEPOLE offers high security level.

Rotational cryptanalysis of round-reduced Keccak

In this paper we attack round-reduced Keccak hash function with a technique called rotational cryptanalysis. We focus on Keccak variants proposed as SHA-3 candidates in the NIST’s contest for a new standard of cryptographic hash function. Our main result is a preimage attack on 4-round Keccak and a 5-round distinguisher on Keccak-f[1600] permutation — the main building block of Keccak hash function.

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Ruumiillinen esine, materiaalinen suku : Tutkimus Pyhä Anna itse kolmantena -aiheisista keskiajan puuveistoksista Suomessa

Embobied Object, Material Family. Late-Medieval Wood Sculptures Depicting Saint Anne with the Virgin and Child in Finland Saint Anne, the mother of the Virgin Mary, was one of the most popular saints in Western Europe in the late Middle Ages. She was often depicted with two other figures, the Virgin and the Christ Child (Anna Selbdritt). The dissertation examines the polychrome wood sculptures showing this motif, with a special focus on those remaining in Finland. It investigates the meanings these sculptures had to their observers in the fifteenth-century Finland. The study sheds light to important material heritage which is little known and offers new insights into the cult and imagery of the holy grandmother. Methodologically the study is based on iconology and post-formalist art history, and it appropriates concepts such as spatiality, sanctity, corporeality, and gender. Taking a comparative approach it knits together larger tendencies and local people and incidents. By conflating methodological domains it renews the ways how fragmentary wood sculptures, lacking documentary written sources, can be contextually interpreted and comprehended. The sculptures are analyzed from three angles. Firstly, the study explores the sculptures by focusing on their materiality and facture, which is to consider them as records of their own making. The analysis provides new information concerning the quantity, location, and current condition of the sculptures and it also elucidates problems regarding attribution, dating, display, and craftsmanship. The book presents the results of the empirical study of 45 Saint Anne groups; these works are individually described in the large Appendix. Secondly, the works are contextualized to the specific historical conditions in which they were observed. The study discusses closely the circumstances in the Turku Cathedral around the shrine of Saint Anne, the popular belief, and the piety of individual persons. The sculptures, deemed as the embodiments of the holy characters, interacted with the devotees. Thirdly, the works are examined within the wider theological and ideological currents of the era centered on the body and Incarnation. Saint Anne with the Virgin and Child motif demonstrated the Carnal Trinity, the motherly side of the Holy Trinity. The dissertation argues that Saint Anne was interpreted as the female counterpart or, in a mythical sense, wife of God. Furthermore, the Child s implicit, simultaneous presence as a suffering or dead man imbues the sculptures with a sense of the Passion, thus associating them with the pietà and the Mater dolorosa motifs. The naked Christ Child underlines him as the offering and, eventually, the Eucharistic wafer. The study suggests that the sculptures mediate continuity and the bloodline between the generations by the intertwined and repeated gestures, clothing and positions of the portrayed figures. Regardless of the ostensible homeliness of the sculptures, so readily reiterated by earlier scholars, these sculptures represented creation and birth through the carnal yet holy mothers.

Approaching Sacred Pregnancy : The Cult of the Visitation and Narrative Altarpieces in Late Fifteenth-Century Florence

The study focuses on the Visitation as a narrative subject of altarpieces in late fifteenth-century Florence. Although the Visitation was a well-known story in both verbal and visual representations since the early medieval period, it became a popular subject of altarpieces only towards the end of the fifteenth century. In this study, the first part provides an overview of the complex religious and historical background to an emerging cult of the Visitation. Devotional practices focusing on the Visitation belong in a context of late medieval Marian devotion and in 1389 a new feast of the Visitation was introduced into the liturgical calendar of the Catholic Church. Because of the ongoing schism within the Catholic Church, the feast was not unanimously accepted across Western Europe until the later part of the fifteenth century. Contrary to a widely disseminated view, the feast of the Visitation cannot be associated with Franciscan spirituality, but was rather a clearly defined Dominican project that primarily emphasised the importance of peace and unity within the Christian Church. Simultaneously with the gradual acceptance of the new feast, visual representations of the Visitation began to appear at the centre of altarpieces. The Visitation exemplifies an increasing preference for narrative subjects within the genre of the altarpiece. The second part of the study presents an analysis of the concept of the narrative altarpiece and highlights the complexities involved in combining a narrative content with the traditional devotional function of the altarpiece. In detailed case studies some prominent art works produced in Florence between 1490 and 1503 are discussed within a framework of contextual analysis, narrative theory and iconography. Altarpieces by Domenico Ghirlandaio, Piero di Cosimo and Mariotto Albertinelli represent visual manifestations of a cult of the Visitation with roots in late medieval devotional practices. At the same time, the altarpieces highlight the multiple functions of altarpieces in a culture where art works responded to a variety of social and religious needs. Building on earlier studies, each case study presents new insights and evidence not considered in previous art historical research.

Tuuleen piirrän nimeni : Daniel Urwindin fragmentaarinen omaelämäkerta Bo Carpelanin romaanissa Alkutuuli

Tutkielma käsittelee Bo Carpelanin romaania Alkutuuli (Urwind 1993) päähenkilö Daniel Urwindin fragmentaarisesti kerrottuna elämäntarinana. Kyse on kahdella aikatasolla etenevästä fiktiivisestä omaelämäkerrasta, joka perustuu viikottaisiin päiväkirjamerkintöihin. Daniel hahmottaa identiteettiään tilaan kytkeytyneiden muistojen sekä oman nimensä avulla leikaten samalla kerronnan jatkuvuuden. Tutkimusongelmana on hahmottaa Danielin kerronnan tavat, kirjoittamisen syyt sekä prosessiin lopputulos. Menneisyyteen kohdistuvan minä-kerronnan analyysi perustuu Dorrit Cohnin Transparent minds -teoksen käsitteistöön. Alkutuulessa esiintyy muistikerronnan ja muistimonologin epäsäännöllistä vuorottelua. Niiden osana on edesmenneiden läheisten upotettuja monologeja, joiden takaa kuultaa Danielin ääni: monologit ovat Danielin kuvittelemia tai referoimia puheita ja ajatuksia, joiden esittäjä on hänen yksinäisen keskustelunsa toinen osapuoli. Omaelämäkertaa käsittelevinä teoreettisina lähteinä ovat ensisijaisesti Päivi Kososen artikkelit sekä hänen tutkimuksensa Elämät sanoissa. Tutkielman tulkinnan kannalta keskeisessä asemassa ovat Bo Carpelanin essee- ja kaunokirjallinen tuotanto. Kirjoittamisen lähtökohtana on päähenkilön identiteettiä horjuttava elämänvaihe. Vaimo Marian lähdettyä vuodeksi Amerikkaan Daniel pyrkii löytämään oman kielensä ja luomaan muistojensa avulla eheämmän kuvan itsestään. Prosessiin kytkeytyy keskeisesti tila - Danielin kulkiessa talossaan, joka on hänen lapsuudenkotinsa, aistitodellisuus toimii mieleenpalauttajana: äänet ja tuoksut johdattavat hänet elämään menneisyyden muistoja uudelleen nykyhetkessä. Samalla talo ja huoneet personifioituvat ja minuus alkaa rakentua tilan kaltaiseksi. Uusien ovien ja huoneiden löytyminen symboloi Danielin muistojen selkeytymistä ja itseymmärryksen syvenemistä. Kirjoittamisen voi tulkita olevan psykoanalyyttinen prosessi, jossa omaelämäkerran minä keskustelee menneisyyden minänsä kanssa. Puhuja odottaa vastausta toiselta, vaikka vastaus löytyy paradoksaalisesti itsestä. Omaelämäkerran moniäänisyyttä korostavat edesmenneiden läheisten läsnäolo, Danielin eri ikävaiheiden identiteetit ja kaksoisolentojen hahmoissa esiintyvät minuudet. Kirjoittamisen avulla Daniel pyrkii pääsemään etäämmälle itsestään ja saavuttamaan minättömyyden tilan, jota käsitellään John Keatsilta peräisin olevan käsitteen "negatiivinen kyky" avulla. Alkutuuli on taiteilijaromaani, jossa taiteilijuutta edustavat siivet ja lentäminen kytkeytyvät mielikuvitukseen ja uusiutumiseen. Danielin tie taiteilijuutta edeltävään minättömyyteen on kuitenkin vaikea ja monet merkit viittaavat diletantin kohtaloon. Unenomaisen logiikan omaavan, fragmentaarisen kerronnan takaa on hahmotettavissa myös lainalaisuuksia. Muiden henkilöiden lyhyet elämäkerrat ovat heidän haavansa paljastavia episodeja, jotka muuttuvat osaksi Danielin elämäntarinaa. Danielin kirjallinen omakuva on montaasi, jossa eri tasossa olevat elementit, nykyhetki ja menneisyys, mielikuvitus, unet ja upotetut monologit rinnastuvat samaan tasoon. Daniel peilaa elettyä ja koettua koomisen peilirakenteen avulla, jossa hänen elämäänsä osallisena olleet menneisyyden henkilöt kulkevat narrikulkueen mukana. Toive eheästä minäkuvasta osoittautuu kuitenkin mahdottomaksi merkityssulkeuman todenvastaisuuden vuoksi. Urwind-nimen pohdinnasta liikkeelle lähtenyt omaelämäkerta päättyy syklistä liikettä mukaillen tilanteeseen, jossa päähenkilö hyväksyy elämän käsittämättömyyden ja luottaa omassa nimessään piilevään voimaan, tuuleen, viitaten samalla myös romaanin nimeen. Avainsanat: Bo Carpelan - muistot - tila - fragmentaarisuus - fiktiivinen omaelämäkerta

Kohti täydellistä hengellisyyttä : Pyhiinvaellus imitaatioperformanssina kolmen keskiaikaisen mystikkonaisen hagiografiassa

Pro gradu -tutkielmassa tarkastellaan kolmen keskiaikaisen mystikkonaisen – Angela Folignolaisen (1248–1309), Dorothea Montaulaisen (1347–1394) ja Margery Kempen (1373–1440) – pyhiinvaelluksilla suorittamien ruumiillisten ja henkisten imitaatioperformanssien suhdetta julkiseen tilaan. Imitaatioperformansseilla viitataan kyseisten naisten harjoittamaan Kristuksen, Neitsyt Marian ja Maria Magdaleenan seuraamiseen. Tutkimuksessa pohditaan kirjallisten representaatioiden valossa performansseja seuranneiden aikalaisten mahdollisia reaktioita ja sitä, vakuuttivatko mystikkojen performanssit yleisönsä. Tutkimuskysymysten kautta valotetaan myös keskiaikaisia käsityksiä sukupuolesta ja sukupuolirooleista. Tutkimuksen pääasiallisena lähdeaineistona käytetään kyseisten naisen pyhimyselämäkertoja. Niiden lisäksi tukeudutaan myös sellaiseen 1200–1400-luvuilla tuotettuun englannin-, ranskan- ja galician-portugalinkieliseen kaunokirjallisuuteen, josta löytyy kuvauksia naispyhiinvaeltajista. Teoreettisena lähtökohtana tutkimuksessa sovelletaan antropologista teoriaa pyhiinvaelluksesta julkisena performanssina, jonka tarkoituksena on rakentaa ja vahvistaa esittäjän identiteettiä. Mystikkonaisten performansseja analysoidaan lisäksi tilan teorioiden valossa. Pääasiallisesti kyseiset teoriat ovat sosiologisia ja antropologisia, joskin tutkimuksessa käytetään myös tutkijan omia julkista tilaa jäsentäviä termejä. Yhtä lailla hyödynnetään folkloristista teoriaa siirtymäriiteistä. Kirjallisten representaatioiden kohdalla analyysin työkaluina käytetään puolestaan kirjallisuustieteilijöiden satiirisen ironian mekanismeja ja funktioita käsitteleviä teorioita. Pro gradu -tutkielmassa päädytään kolmenlaisiin johtopäätelmiin. Ensinnäkin lähdeaineistosta käy ilmi, että Angela Folignolaisen, Dorothea Montaulaisen ja Margery Kempen performanssien suhde julkiseen tilaan oli looginen. Ulospäin näkyvät ruumiilliset performanssit suoritettiin usein sellaisessa julkisessa tilassa, jossa potentiaalista yleisöä oli tarjolla eniten. Ulospäin vain vähän näkyvät henkiset performanssit puolestaan tapahtuivat usein tilassa, jossa yleisön vähyyttä kompensoi vahva pyhyyden tuntu. Pyhiinvaellus tarjosikin naisille mahdollisuuden toteuttaa mystiikan nk. toista vaihetta, osittain myös kolmatta, ja vahvistaa siten täydelliseen hengellisyyteen pyrkivän hengellisen maallikkonaisen identiteettiä. Lähdeaineistosta käy toiseksi ilmi se, että nykytutkimuksessa on painotettu liian vähän ruumiillisuuden merkitystä naishengellisyydessä. Etenkin Dorothea Montaulainen seurasi Kristuksen ja Maria Magdaleenan esimerkkiä huomattavan usein kehossa asti tuntuvien performanssien avulla. Kolmas lähdeaineiston paljastama seikka liittyy yleisöön. On mahdollista, että mystikoiden ei onnistunut vakuuttaa performansseja seurannutta oppinutta, ”porvarillista” miesyleisöä. Kirjallisten representaatioiden valossa näyttää siltä, että se ei välttämättä hyväksynyt maskuliiniseksi koetussa julkisessa tilassa liikkunutta, sukupuolisia rajoja ylittänyttä naista. Mystikot saattoivat myös edustaa seksuaalista uhkaa, sillä yleisö yhdisti julkisessa tilassa liikkuneen naisen ruumiillisuuteen ja aistillisuuteen.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

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.