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

@article{Shungin2015NewGL,
  title={New genetic loci link adipose and insulin biology to body fat distribution},
  author={Dmitry Shungin and Thomas W. Winkler and Damien C. Croteau-Chonka and Teresa Ferreira and Adam E. Locke and Reedik M{\"a}gi and Rona J. Strawbridge and Tune H. Pers and Krista Fischer and Anne E. Justice and Tsegaselassie Workalemahu and Joseph Wu and Martin L Buchkovich and Nancy L. Heard-Costa and Tamara S. Roman and Alexander W. Drong and Ci Song and Stefan Gustafsson and Felix R. Day and T{\~o}nu Esko and Tove Fall and Zolt{\'a}n Kutalik and Jian’an Luan and Joshua C. Randall and Andr{\'e} Scherag and Sailaja Vedantam and Andrew R. Wood and Jin Chen and Rudolf S. N. Fehrmann and Juha Karjalainen and Bratati Kahali and Ching‐Ti Liu and Ellen M. Schmidt and Devin M Absher and Najaf Amin and Denise Anderson and Marian Beekman and Jennifer L. Bragg-Gresham and Steven Buyske and Ayşe Demirkan and Georg B. Ehret and Mary F. Feitosa and Anuj Goel and Anne U. Jackson and Toby Johnson and Marcus Edi Kleber and Kati Kristiansson and Massimo Mangino and Irene Mateo Leach and Carolina Medina-Gomez and Cameron Palmer and Dorota Pasko and Sonali Pechlivanis and Marjolein J. Peters and Inga Prokopenko and Alena Stan{\vc}{\'a}kov{\'a} and Yun Ju Sung and Toshiko Tanaka and Alexander Teumer and Jana V. van Vliet-Ostaptchouk and Loic Yengo and Weihua Zhang and Eva Albrecht and Johan {\"A}rnl{\"o}v and Gillian M. Arscott and Stefania Bandinelli and Amy Barrett and Claire Bellis and Amanda Bennett and Christian Berne and Matthias Bl{\"u}her and Stefan B{\"o}hringer and Fabrice Bonnet and Yvonne B{\"o}ttcher and Marcel Bruinenberg and Delia B. Carba and Ida Henriette Caspersen and Robert J. Clarke and E. Warwick Daw and Joris Deelen and Ewa Deelman and Graciela E. Delgado and Alex S. F. Doney and Niina Eklund and Michael R. Erdos and Karol Estrada and Elodie Eury and Nele Friedrich and Melissa E. Garcia and Vilmantas Giedraitis and Bruna Gigante and Alan S. Go and Alain Golay and Harald Grallert and Tanja B. Grammer and J{\"u}rgen Gr{\"a}ssler and Jagvir Grewal and Christopher J. Groves and Toomas Haller and Göran Hallmans and Catharina A. Hartman and Maija Hassinen and Caroline Hayward and Kauko Heikkil{\"a} and Karl‐Heinz Herzig and Quinta Helmer and Hans L. Hillege and Oddgeir Lingaas Holmen and Steven C. Hunt and Aaron Isaacs and Till Ittermann and Alan L James and Ingegerd Johansson and Thorhildur Juliusdottir and Ioanna Panagiota Kalafati and Leena Kinnunen and Wolfgang Koenig and Ishminder K. Kooner and Wolfgang Kratzer and Claudia Lamina and Karin Leander and Nanette R. Lee and Peter Lichtner and Lars Lind and Jaana Lindstr{\"o}m and St{\'e}phane Lobbens and Mattias Lorentzon and François Mach and Patrik K. E. Magnusson and Anubha Mahajan and Wendy L McArdle and Cristina Menni and Sigrun Merger and Evelin Mihailov and Lili Milani and Rebecca Mills and Alireza Moayyeri and Keri L. Monda and Simon P. Mooijaart and Thomas W. M{\"u}hleisen and Antonella Mulas and Gabriele M{\"u}ller and Martina M{\"u}ller-Nurasyid and Ramaiah Nagaraja and Mike A. Nalls and Narisu Narisu and Nicola Glorioso and Ilja Maria Nolte and Matthias Olden and Nigel William Rayner and Frida Renstrom and Janina S. Ried and Neil R. Robertson and Lynda M Rose and Serena Sanna and Hubert Scharnagl and Salome Scholtens and Bengt Sennblad and Thomas Seufferlein and Colleen M. Sitlani and Albert Vernon Smith and Kathleen E. Stirrups and Heather M. Stringham and Johan Sundstr{\"o}m and Morris A. Swertz and Amy J. Swift and Ann-Christine Syv{\"a}nen and Bamidele O. Tayo and Barbara Thorand and Gudmar Thorleifsson and Andreas Tomaschitz and Chiara Troffa and Floor V. A. van Oort and Niek Verweij and Judith M. Vonk and Lindsay L. Waite and Roman Wennauer and Tom Wilsgaard and Mary K. Wojczynski and Andrew Wong and Qunyuan Zhang and Jing Hua Zhao and Eoin P. Brennan and Murim Choi and Per Eriksson and Lasse Folkersen and Anders Franco‐Cereceda and Ali G. Gharavi and {\AA}sa K. Hedman and Marie-France Hivert and Jinyan Huang and Stavroula Kanoni and Fredrik Karpe and Sarah Keildson and Krzysztof Kiryluk and Liming Liang and Richard P. Lifton and Baoshan Ma and Amy Jayne McKnight and Ruth McPherson and Andres Metspalu and Josine L. Min and Miriam F. Moffatt and Grant W. Montgomery and Joanne M. Murabito and George Nicholson and Dale R. Nyholt and Christian Olsson and John R. B. Perry and Eva Reinmaa and Rany M. Salem and Niina Sandholm and Eric E. Schadt and Robert A. Scott and Lisette Stolk and Edgar E. Vallejo and Harm-Jan Westra and Krina T. Zondervan and Philippe Amouyel and Dominique Arveiler and Stephan J. L. Bakker and John P. Beilby and Richard N. Bergman and John Blangero and Morris J. Brown and Michel Burnier and Harry Campbell and Aravinda Chakravarti and Peter S. Chines and Simone Claudi-Boehm and Francis S. Collins and Dana C. Crawford and John Danesh and Ulf de Faire and Eco J. C. de Geus and Marcus D{\"o}rr and Raimund Erbel and Johan Gunnar Eriksson and Martin Farrall and Ele Ferrannini and Jean Ferri{\`e}res and Nita G. Forouhi and Terrence E Forrester and Oscar H. Franco and Ron T. Gansevoort and Christian Gieger and Vilmundur G. Gudnason and Christopher A. Haiman and Tamara B. Harris and Andrew T. Hattersley and Markku Heliövaara and Andrew A. Hicks and Aroon D. Hingorani and Wolfgang U. Hoffmann and Albert Hofman and Georg Homuth and Steve E. Humphries and Elina Hypp{\"o}nen and Thomas Illig and Marjo-Riitta Jarvelin and Berit Johansen and Pekka Jousilahti and Antti M Jula and Jaakko A Kaprio and Frank Kee and Sirkka Keinanen-Kiukaanniemi and Jaspal S Kooner and Charles L. Kooperberg and Peter Kovacs and Aldi T. Kraja and Meena Kumari and Kari Kuulasmaa and Johanna Kuusisto and Timo A. Lakka and Claudia Langenberg and Lo{\"i}c Le Marchand and Terho Lehtim{\"a}ki and Valeriya Lyssenko and Satu M{\"a}nnist{\"o} and Andr{\'e} Marette and Tara Cox Matise and Colin A Mckenzie and Barbara McKnight and Arthur William Musk and Stefan M{\"o}hlenkamp and Andrew D. Morris and Mari Nelis and Claes Ohlsson and Albertine J. Oldehinkel and Ken K. Ong and Lyle J. Palmer and Brenda W.J.H. Penninx and Annette Peters and Peter Paul Pramstaller and Olli T. Raitakari and Tuomo Rankinen and D. C. Rao and Treva K. Rice and Paul M. Ridker and Marylyn DeRiggi Ritchie and Igor Rudan and Veikko V Salomaa and Nilesh J. Samani and Jouko Saramies and Mark A. Sarzynski and Peter E H Schwarz and Alan R. Shuldiner and Jan A. Staessen and Valgerdur Steinthorsdottir and Ronald P Stolk and Konstantin Strauch and Anke Tönjes and Angelo Tremblay and Elena Tremoli and Marie-Claude Vohl and Uwe V{\"o}lker and Peter Vollenweider and James F. Wilson and Jacqueline C. M. Witteman and Linda S Adair and Murielle Bochud and Bernhard Otto Boehm and Stefan R. Bornstein and Claude Bouchard and Stéphane Cauchi and Mark J. Caulfield and John C Chambers and Daniel I. Chasman and Richard S. Cooper and George V. Dedoussis and Luigi Ferrucci and Philippe Froguel and Hans J{\"o}rgen Grabe and Anders Hamsten and Jennie Hui and Kristian Hveem and Karl-Heinz J{\"o}ckel and Mika Kivimaki and Diana Kuh and Markku Laakso and Yongmei Liu and Winfried M{\"a}rz and Patricia B. Munroe and Inger Nj{\o}lstad and Ben A. Oostra and Colin N. A. Palmer and Nancy L. Pedersen and Markus Perola and Louis P{\'e}russe and Ulrike Peters and Christine Power and Thomas Quertermous and Rainer Rauramaa and Fernando Rivadeneira and Timo E. Saaristo and Danish Saleheen and Juha P. Sinisalo and Pieternella E Slagboom and Harold Snieder and Tim D. Spector and K{\'a}ri Stef{\'a}nsson and Michael Stumvoll and Jaakko Tuomilehto and Andr{\'e} G. Uitterlinden and Matti Uusitupa and Pim van der Harst and Giovanni Veronesi and Mark Walker and Nicholas J. Wareham and Hugh C. Watkins and Heinz-Erich Wichmann and Gonçalo R. Abecasis and Themistocles L. Assimes and Sonja I. Berndt and Michael Boehnke and Ingrid B. Borecki and Panos Deloukas and Lude Franke and Timothy M. Frayling and Leif C. Groop and David J. Hunter and Robert C. Kaplan and Jeffrey R. O’Connell and Lu Qi and David Schlessinger and David P. Strachan and Unnur Thorsteinsd{\'o}ttir and Cornelia M. van Duijn and Cristen J. Willer and Peter M. Visscher and Jian Yang and Joel N. Hirschhorn and M. Carola Zillikens and Mark I. McCarthy and Elizabeth K. Speliotes and Kari E. North and Caroline S Fox and In{\^e}s Barroso and Paul W. Franks and Erik Ingelsson and Iris M. Heid and Ruth J. F. Loos and L. Adrienne Cupples and Andrew P. Morris and Cecilia M. Lindgren and Karen L. Mohlke},
  journal={Nature},
  year={2015},
  volume={518},
  pages={187 - 196}
}
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… 

Genomics of body fat distribution.

TLDR
The current knowledge of genomic basis of body fat distribution is reviewed, suggesting that both sexes share potentially different biological architecture in traits related to bodyfat distribution.

Genome-wide association study of body fat distribution identifies adiposity loci and sex-specific genetic effects

TLDR
It is implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues as well as extracellular matrix maintenance and remodeling, and the effects of 37 associated variants are stronger in females compared to males.

Shared genetic loci for body fat storage and adipocyte lipolysis in humans

TLDR
Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts.

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

TLDR
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 provide strong support for a role of the central nervous system in obesity susceptibility.

Numerous Genes in Loci Associated With Body Fat Distribution Are Linked to Adipose Function

TLDR
The genetic influence on body fat distribution could be mediated via several specific alterations in adipose tissue morphology and function, which in turn may influence the development of type 2 diabetes.

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

TLDR
The loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

PROTEIN-CODING VARIANTS IMPLICATE NOVEL GENES RELATED TO LIPID HOMEOSTASIS CONTRIBUTING TO BODY FAT DISTRIBUTION

TLDR
A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

Genome-wide association study of body fat distribution identifies novel loci and sex-specific effects

TLDR
These findings provide evidence for multiple loci that affect the distribution of body fat to discrete compartments of the human body, and highlight that genetic effects differ between men and women, in particular for distribution ofBody fat to the legs and trunk.

Sexual dimorphisms in genetic loci linked to body fat distribution

TLDR
Research that specifically focuses on sexual dimorphism in fat distribution can provide novel insights into human physiology and into the development of obesity and its comorbidities, as well as yield biological clues that will aid in the improvement of disease prevention and treatment.

Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.

...

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