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

doi:10.1038/ncomms10495

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Justice, Anne E.University of North Carolina,Geisinger Health System (author)

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Article/chapterEnglish2019

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2019-02-18
Nature Publishing Group,2019
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LIBRIS-ID:oai:DiVA.org:umu-157574
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-157574URI
https://doi.org/10.1038/s41588-018-0334-2DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-379344URI
https://lup.lub.lu.se/record/e480e762-4ec0-490f-8de5-8201f81cca66URI

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Language:English
Summary in:English

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For complete list of authors see http://dx.doi.org/10.1038/s41588-018-0334-2
Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

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Karaderi, Tugce (author)
Highland, Heather M. (author)
Lind, LarsUppsala universitet,Klinisk epidemiologi(Swepub:uu)larslind (author)
Graff, Mariaelisa (author)
Lu, Yingchang (author)
Turcot, Valerie (author)
Auer, Paul L. (author)
Fine, Rebecca S. (author)
Guo, Xiuqing (author)
Schurmann, Claudia (author)
Lempradl, Adelheid (author)
Marouli, Eirini (author)
Mahajan, Anubha (author)
Winkler, Thomas W. (author)
Locke, Adam E. (author)
Medina-Gomez, Carolina (author)
Esko, Tonu (author)
Vedantam, Sailaja (author)
Giri, Ayush (author)
Lo, Ken Sin (author)
Alfred, Tamuno (author)
Mudgal, Poorva (author)
Ng, Maggie C. Y. (author)
Heard-Costa, Nancy L. (author)
Feitosa, Mary F. (author)
Manning, Alisa K. (author)
Willems, Sara M. (author)
Sivapalaratnam, Suthesh (author)
Abecasis, Goncalo (author)
Alam, Dewan S. (author)
Allison, Matthew (author)
Amouyel, Philippe (author)
Arzumanyanm, Zorayr (author)
Balkau, Beverley (author)
Bastarache, Lisa (author)
Bergmann, Sven (author)
Bielak, Lawrence F. (author)
Blueher, Matthias (author)
Boehnke, Michael (author)
Boeing, Heiner (author)
Boerwinkle, Eric (author)
Boeger, Carsten A. (author)
Bork-Jensen, Jette (author)
Bottinger, Erwin P. (author)
Bowden, Donald W. (author)
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Broer, Linda (author)
Burt, Amber A. (author)
Butterworth, Adam S. (author)
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Cesana, Giancarlo (author)
Chambers, John C. (author)
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Chowdhury, Rajiv (author)
Christensen, Cramer (author)
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Cook, James P. (author)
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Dedoussis, George (author)
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Denny, Josh C. (author)
Di Angelantonio, Emanuele (author)
Doerr, Marcus (author)
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Dunning, Alison M. (author)
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Evangelou, EvangelosUniversity of North Carolina (author)
Farmaki, Aliki-Eleni (author)
Feng, Shuang (author)
Ferrannini, Ele (author)
Ferrieres, Jean (author)
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Fornage, Myriam (author)
Fox, Caroline S. (author)
Franks, Paul W.Umeå University,Lund University,Lunds universitet,Umeå universitet,Avdelningen för medicin,Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf (author)
Friedrich, Nele (author)
Gan, Wei (author)
Gandin, Ilaria (author)
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Giedraitis, VilmantasUppsala universitet,Geriatrik(Swepub:uu)vigie517 (author)
Girotto, Giorgia (author)
Gorski, Mathias (author)
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Moitry, MarieUniversity of Oxford (author)
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White, Harvey D. (author)
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De Bakker, Paul Iw (author)
Caulfield, Mark J. (author)
Mller-Nurasyid, Martina (author)
University of North CarolinaGeisinger Health System (creator_code:org_t)
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