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

Détails

Ressource 1Télécharger: 30778226_BIB_3FE73F14651D.pdf (921.20 [Ko])
Etat: Public
Version: Author's accepted manuscript
Licence: Non spécifiée
ID Serval
serval:BIB_3FE73F14651D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.
Périodique
Nature genetics
Auteur(s)
Justice A.E., Karaderi T., Highland H.M., Young K.L., Graff M., Lu Y., Turcot V., Auer P.L., Fine R.S., Guo X., Schurmann C., Lempradl A., Marouli E., Mahajan A., Winkler T.W., Locke A.E., Medina-Gomez C., Esko T., Vedantam S., Giri A., Lo K.S., Alfred T., Mudgal P., Ng MCY, Heard-Costa N.L., Feitosa M.F., Manning A.K., Willems S.M., Sivapalaratnam S., Abecasis G., Alam D.S., Allison M., Amouyel P., Arzumanyan Z., Balkau B., Bastarache L., Bergmann S., Bielak L.F., Blüher M., Boehnke M., Boeing H., Boerwinkle E., Böger C.A., Bork-Jensen J., Bottinger E.P., Bowden D.W., Brandslund I., Broer L., Burt A.A., Butterworth A.S., Caulfield M.J., Cesana G., Chambers J.C., Chasman D.I., Chen Y.I., Chowdhury R., Christensen C., Chu A.Y., Collins F.S., Cook J.P., Cox A.J., Crosslin D.S., Danesh J., de Bakker PIW, Denus S., Mutsert R., Dedoussis G., Demerath E.W., Dennis J.G., Denny J.C., Angelantonio E.D., Dörr M., Drenos F., Dubé M.P., Dunning A.M., Easton D.F., Elliott P., Evangelou E., Farmaki A.E., Feng S., Ferrannini E., Ferrieres J., Florez J.C., Fornage M., Fox C.S., Franks P.W., Friedrich N., Gan W., Gandin I., Gasparini P., Giedraitis V., Girotto G., Gorski M., Grallert H., Grarup N., Grove M.L., Gustafsson S., Haessler J., Hansen T., Hattersley A.T., Hayward C., Heid I.M., Holmen O.L., Hovingh G.K., Howson JMM, Hu Y., Hung Y.J., Hveem K., Ikram M.A., Ingelsson E., Jackson A.U., Jarvik G.P., Jia Y., Jørgensen T., Jousilahti P., Justesen J.M., Kahali B., Karaleftheri M., Kardia SLR, Karpe F., Kee F., Kitajima H., Komulainen P., Kooner J.S., Kovacs P., Krämer B.K., Kuulasmaa K., Kuusisto J., Laakso M., Lakka T.A., Lamparter D., Lange L.A., Langenberg C., Larson E.B., Lee N.R., Lee W.J., Lehtimäki T., Lewis C.E., Li H., Li J., Li-Gao R., Lin L.A., Lin X., Lind L., Lindström J., Linneberg A., Liu C.T., Liu D.J., Luan J., Lyytikäinen L.P., MacGregor S., Mägi R., Männistö S., Marenne G., Marten J., Masca NGD, McCarthy M.I., Meidtner K., Mihailov E., Moilanen L., Moitry M., Mook-Kanamori D.O., Morgan A., Morris A.P., Müller-Nurasyid M., Munroe P.B., Narisu N., Nelson C.P., Neville M., Ntalla I., O'Connell J.R., Owen K.R., Pedersen O., Peloso G.M., Pennell C.E., Perola M., Perry J.A., Perry JRB, Pers T.H., Ewing A., Polasek O., Raitakari O.T., Rasheed A., Raulerson C.K., Rauramaa R., Reilly D.F., Reiner A.P., Ridker P.M., Rivas M.A., Robertson N.R., Robino A., Rudan I., Ruth K.S., Saleheen D., Salomaa V., Samani N.J., Schreiner P.J., Schulze M.B., Scott R.A., Segura-Lepe M., Sim X., Slater A.J., Small K.S., Smith B.H., Smith J.A., Southam L., Spector T.D., Speliotes E.K., Stefansson K., Steinthorsdottir V., Stirrups K.E., Strauch K., Stringham H.M., Stumvoll M., Sun L., Surendran P., Swart KMA, Tardif J.C., Taylor K.D., Teumer A., Thompson D.J., Thorleifsson G., Thorsteinsdottir U., Thuesen B.H., Tönjes A., Torres M., Tsafantakis E., Tuomilehto J., Uitterlinden A.G., Uusitupa M., van Duijn C.M., Vanhala M., Varma R., Vermeulen S.H., Vestergaard H., Vitart V., Vogt T.F., Vuckovic D., Wagenknecht L.E., Walker M., Wallentin L., Wang F., Wang C.A., Wang S., Wareham N.J., Warren H.R., Waterworth D.M., Wessel J., White H.D., Willer C.J., Wilson J.G., Wood A.R., Wu Y., Yaghootkar H., Yao J., Yerges-Armstrong L.M., Young R., Zeggini E., Zhan X., Zhang W., Zhao J.H., Zhao W., Zheng H., Zhou W., Zillikens M.C., Rivadeneira F., Borecki I.B., Pospisilik J.A., Deloukas P., Frayling T.M., Lettre G., Mohlke K.L., Rotter J.I., Kutalik Z., Hirschhorn J.N., Cupples L.A., Loos RJF, North K.E., Lindgren C.M.
Collaborateur(s)
CHD Exome+ Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, InterAct, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
03/2019
Peer-reviewed
Oui
Volume
51
Numéro
3
Pages
452-469
Langue
anglais
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Animals, Body Fat Distribution/methods, Body Mass Index, Case-Control Studies, Drosophila/genetics, Exome/genetics, Female, Gene Frequency/genetics, Genetic Predisposition to Disease/genetics, Genetic Variation/genetics, Genome-Wide Association Study/methods, Homeostasis/genetics, Humans, Lipids/genetics, Male, Proteins/genetics, Risk Factors, Waist-Hip Ratio/methods
Pubmed
Web of science
Création de la notice
28/02/2019 14:52
Dernière modification de la notice
30/04/2021 6:09
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