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

dc.contributor.authorJustice, AE
dc.contributor.authorKaraderi, T
dc.contributor.authorHighland, HM
dc.contributor.authorYoung, KL
dc.contributor.authorGraff, M
dc.contributor.authorLu, Y
dc.contributor.authorTurcot, V
dc.contributor.authorAuer, PL
dc.contributor.authorFine, RS
dc.contributor.authorGuo, X
dc.contributor.authorSchurmann, C
dc.contributor.authorLempradl, A
dc.contributor.authorMarouli, E
dc.contributor.authorMahajan, A
dc.contributor.authorWinkler, TW
dc.contributor.authorLocke, AE
dc.contributor.authorMedina-Gomez, C
dc.contributor.authorEsko, T
dc.contributor.authorVedantam, S
dc.contributor.authorGiri, A
dc.contributor.authorLo, KS
dc.contributor.authorAlfred, T
dc.contributor.authorMudgal, P
dc.contributor.authorNg, MCY
dc.contributor.authorHeard-Costa, NL
dc.contributor.authorFeitosa, MF
dc.contributor.authorManning, AK
dc.contributor.authorWillems, SM
dc.contributor.authorSivapalaratnam, S
dc.contributor.authorAbecasis, G
dc.contributor.authorAlam, DS
dc.contributor.authorAllison, M
dc.contributor.authorAmouyel, P
dc.contributor.authorArzumanyan, Z
dc.contributor.authorBalkau, B
dc.contributor.authorBastarache, L
dc.contributor.authorBergmann, S
dc.contributor.authorBielak, LF
dc.contributor.authorBlüher, M
dc.contributor.authorBoehnke, M
dc.contributor.authorBoeing, H
dc.contributor.authorBoerwinkle, E
dc.contributor.authorBöger, CA
dc.contributor.authorBork-Jensen, J
dc.contributor.authorBottinger, EP
dc.contributor.authorBowden, DW
dc.contributor.authorBrandslund, I
dc.contributor.authorBroer, L
dc.contributor.authorBurt, AA
dc.contributor.authorButterworth, AS
dc.contributor.authorCaulfield, MJ
dc.contributor.authorCesana, G
dc.contributor.authorChambers, JC
dc.contributor.authorChasman, DI
dc.contributor.authorChen, Y-DI
dc.contributor.authorChowdhury, R
dc.contributor.authorChristensen, C
dc.contributor.authorChu, AY
dc.contributor.authorCollins, FS
dc.contributor.authorCook, JP
dc.contributor.authorCox, AJ
dc.contributor.authorCrosslin, DS
dc.contributor.authorDanesh, J
dc.contributor.authorde Bakker, PIW
dc.contributor.authorDenus, SD
dc.contributor.authorMutsert, RD
dc.contributor.authorDedoussis, G
dc.contributor.authorDemerath, EW
dc.contributor.authorDennis, JG
dc.contributor.authorDenny, JC
dc.contributor.authorAngelantonio, ED
dc.contributor.authorDörr, M
dc.contributor.authorDrenos, F
dc.contributor.authorDubé, M-P
dc.contributor.authorDunning, AM
dc.contributor.authorEaston, DF
dc.contributor.authorElliott, P
dc.contributor.authorEvangelou, E
dc.contributor.authorFarmaki, A-E
dc.contributor.authorFeng, S
dc.contributor.authorFerrannini, E
dc.contributor.authorFerrieres, J
dc.contributor.authorFlorez, JC
dc.contributor.authorFornage, M
dc.contributor.authorFox, CS
dc.contributor.authorFranks, PW
dc.contributor.authorFriedrich, N
dc.contributor.authorGan, W
dc.contributor.authorGandin, I
dc.contributor.authorGasparini, P
dc.contributor.authorGiedraitis, V
dc.contributor.authorGirotto, G
dc.contributor.authorGorski, M
dc.contributor.authorGrallert, H
dc.contributor.authorGrarup, N
dc.contributor.authorGrove, ML
dc.contributor.authorGustafsson, S
dc.contributor.authorHaessler, J
dc.contributor.authorHansen, T
dc.contributor.authorHattersley, AT
dc.contributor.authorHayward, C
dc.contributor.authorHeid, IM
dc.contributor.authorHolmen, OL
dc.contributor.authorHovingh, GK
dc.contributor.authorHowson, JMM
dc.contributor.authorHu, Y
dc.contributor.authorHung, Y-J
dc.contributor.authorHveem, K
dc.contributor.authorIkram, MA
dc.contributor.authorIngelsson, E
dc.contributor.authorJackson, AU
dc.contributor.authorJarvik, GP
dc.contributor.authorJia, Y
dc.contributor.authorJørgensen, T
dc.contributor.authorJousilahti, P
dc.contributor.authorJustesen, JM
dc.contributor.authorKahali, B
dc.contributor.authorKaraleftheri, M
dc.contributor.authorKardia, SLR
dc.contributor.authorKarpe, F
dc.contributor.authorKee, F
dc.contributor.authorKitajima, H
dc.contributor.authorKomulainen, P
dc.contributor.authorKooner, JS
dc.contributor.authorKovacs, P
dc.contributor.authorKrämer, BK
dc.contributor.authorKuulasmaa, K
dc.contributor.authorKuusisto, J
dc.contributor.authorLaakso, M
dc.contributor.authorLakka, TA
dc.contributor.authorLamparter, D
dc.contributor.authorLange, LA
dc.contributor.authorLangenberg, C
dc.contributor.authorLarson, EB
dc.contributor.authorLee, NR
dc.contributor.authorLee, W-J
dc.contributor.authorLehtimäki, T
dc.contributor.authorLewis, CE
dc.contributor.authorLi, H
dc.contributor.authorLi, J
dc.contributor.authorLi-Gao, R
dc.contributor.authorLin, L-A
dc.contributor.authorLin, X
dc.contributor.authorLind, L
dc.contributor.authorLindström, J
dc.contributor.authorLinneberg, A
dc.contributor.authorLiu, C-T
dc.contributor.authorLiu, DJ
dc.contributor.authorLuan, J
dc.contributor.authorLyytikäinen, L-P
dc.contributor.authorMacGregor, S
dc.contributor.authorMägi, R
dc.contributor.authorMännistö, S
dc.contributor.authorMarenne, G
dc.contributor.authorMarten, J
dc.contributor.authorMasca, NGD
dc.contributor.authorMcCarthy, MI
dc.contributor.authorMeidtner, K
dc.contributor.authorMihailov, E
dc.contributor.authorMoilanen, L
dc.contributor.authorMoitry, M
dc.contributor.authorMook-Kanamori, DO
dc.contributor.authorMorgan, A
dc.contributor.authorMorris, AP
dc.contributor.authorMüller-Nurasyid, M
dc.contributor.authorMunroe, PB
dc.contributor.authorNarisu, N
dc.contributor.authorNelson, CP
dc.contributor.authorNeville, M
dc.contributor.authorNtalla, I
dc.contributor.authorO'Connell, JR
dc.contributor.authorOwen, KR
dc.contributor.authorPedersen, O
dc.contributor.authorPeloso, GM
dc.contributor.authorPennell, CE
dc.contributor.authorPerola, M
dc.contributor.authorPerry, JA
dc.contributor.authorPerry, JRB
dc.contributor.authorPers, TH
dc.contributor.authorEwing, A
dc.contributor.authorPolasek, O
dc.contributor.authorRaitakari, OT
dc.contributor.authorRasheed, A
dc.contributor.authorRaulerson, CK
dc.contributor.authorRauramaa, R
dc.contributor.authorReilly, DF
dc.contributor.authorReiner, AP
dc.contributor.authorRidker, PM
dc.contributor.authorRivas, MA
dc.contributor.authorRobertson, NR
dc.contributor.authorRobino, A
dc.contributor.authorRudan, I
dc.contributor.authorRuth, KS
dc.contributor.authorSaleheen, D
dc.contributor.authorSalomaa, V
dc.contributor.authorSamani, NJ
dc.contributor.authorSchreiner, PJ
dc.contributor.authorSchulze, MB
dc.contributor.authorScott, RA
dc.contributor.authorSegura-Lepe, M
dc.contributor.authorSim, X
dc.contributor.authorSlater, AJ
dc.contributor.authorSmall, KS
dc.contributor.authorSmith, BH
dc.contributor.authorSmith, JA
dc.contributor.authorSoutham, L
dc.contributor.authorSpector, TD
dc.contributor.authorSpeliotes, EK
dc.contributor.authorStefansson, K
dc.contributor.authorSteinthorsdottir, V
dc.contributor.authorStirrups, KE
dc.contributor.authorStrauch, K
dc.contributor.authorStringham, HM
dc.contributor.authorStumvoll, M
dc.contributor.authorSun, L
dc.contributor.authorSurendran, P
dc.contributor.authorSwart, KMA
dc.contributor.authorTardif, J-C
dc.contributor.authorTaylor, KD
dc.contributor.authorTeumer, A
dc.contributor.authorThompson, DJ
dc.contributor.authorThorleifsson, G
dc.contributor.authorThorsteinsdottir, U
dc.contributor.authorThuesen, BH
dc.contributor.authorTönjes, A
dc.contributor.authorTorres, M
dc.contributor.authorTsafantakis, E
dc.contributor.authorTuomilehto, J
dc.contributor.authorUitterlinden, AG
dc.contributor.authorUusitupa, M
dc.contributor.authorvan Duijn, CM
dc.contributor.authorVanhala, M
dc.contributor.authorVarma, R
dc.contributor.authorVermeulen, SH
dc.contributor.authorVestergaard, H
dc.contributor.authorVitart, V
dc.contributor.authorVogt, TF
dc.contributor.authorVuckovic, D
dc.contributor.authorWagenknecht, LE
dc.contributor.authorWalker, M
dc.contributor.authorWallentin, L
dc.contributor.authorWang, F
dc.contributor.authorWang, CA
dc.contributor.authorWang, S
dc.contributor.authorWareham, NJ
dc.contributor.authorWarren, HR
dc.contributor.authorWaterworth, DM
dc.contributor.authorWessel, J
dc.contributor.authorWhite, HD
dc.contributor.authorWiller, CJ
dc.contributor.authorWilson, JG
dc.contributor.authorWood, AR
dc.contributor.authorWu, Y
dc.contributor.authorYaghootkar, H
dc.contributor.authorYao, J
dc.contributor.authorYerges-Armstrong, LM
dc.contributor.authorYoung, R
dc.contributor.authorZeggini, E
dc.contributor.authorZhan, X
dc.contributor.authorZhang, W
dc.contributor.authorZhao, JH
dc.contributor.authorZhao, W
dc.contributor.authorZheng, H
dc.contributor.authorZhou, W
dc.contributor.authorZillikens, MC
dc.contributor.authorCHD Exome+ Consortium
dc.contributor.authorCohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
dc.contributor.authorEPIC-CVD Consortium
dc.contributor.authorExomeBP Consortium
dc.contributor.authorGlobal Lipids Genetic Consortium
dc.contributor.authorGoT2D Genes Consortium
dc.contributor.authorInterAct
dc.contributor.authorReproGen Consortium
dc.contributor.authorT2D-Genes Consortium
dc.contributor.authorMAGIC Investigators
dc.contributor.authorRivadeneira, F
dc.contributor.authorBorecki, IB
dc.contributor.authorPospisilik, JA
dc.contributor.authorDeloukas, P
dc.contributor.authorFrayling, TM
dc.contributor.authorLettre, G
dc.contributor.authorMohlke, KL
dc.contributor.authorRotter, JI
dc.contributor.authorKutalik, Z
dc.contributor.authorHirschhorn, JN
dc.contributor.authorCupples, LA
dc.contributor.authorLoos, RJF
dc.contributor.authorNorth, KE
dc.contributor.authorLindgren, CM
dc.date.accessioned2019-03-13T11:52:58Z
dc.date.available2018-12-17
dc.date.available2019-03-13T11:52:58Z
dc.date.issued2019-02-18
dc.identifier.citationJustice, A. E., et al. (2019). "Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution." Nature Genetics 51(3): 452-469.en_US
dc.identifier.issn1061-4036
dc.identifier.urihttps://qmro.qmul.ac.uk/xmlui/handle/123456789/56167
dc.descriptionPost-prints subject to Springer Nature re-use termsen_US
dc.description.abstractBody-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.en_US
dc.description.sponsorshipH.D.W. has the following financial and non-financial competing interests to declare: research grants: Sanofi Aventis; Eli Lilly; NIH; Omthera Pharmaceuticals, Pfizer, Elsai Inc. AstraZeneca; DalCor and Services; lecture fees: Sanofi Aventis; advisory boards: Acetelion, Sirtex, CSL Boehring. J.D. has received grants from AstraZeneca, Biogen, Merck, Novartis and Pfizeren_US
dc.languageeng
dc.language.isoenen_US
dc.publisherNature Research (part of Springer Nature)en_US
dc.relation.ispartofNat Genet
dc.subjectBody-fat distributionen_US
dc.subjectcardiovascular healthen_US
dc.subjectwaist-to-hip ratioen_US
dc.subjectbody mass indexen_US
dc.titleProtein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.en_US
dc.typeArticleen_US
dc.rights.holder2019. The authors
dc.identifier.doi10.1038/s41588-018-0334-2
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30778226en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US
dcterms.dateAccepted2018-12-17
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US


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