biostudies-literatureStefanucci LBLRD VABritish Heart FoundationNNF Center for Basic Metabolic ResearchWellcome Trust1083-1095.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617389biostudies-literatureUnknown5(9)<h4>Background</h4>Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.<h4>Methods</h4>We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-oMed (New York, N.Y.)SMIM1 absence is associated with reduced energy expenditure and excess weight.PMC7617389210755/Z/18/ZHansen Group219496/Z/19/ZFS/18/53/33863I01 BX004821I01 BX003340219496RG/18/7/33636210755Bowden DWNeville MJKawaguchi TVerweij NBrunak SZhao JHKleber MEMatsuda FFrary ATonjes ASchurmann CSchurmann Ade Haan HGSandow KBornstein SRVan Vliet-Ostaptchouk JVZemunik TGroop LSaaristo TEWalker MWalker LErber WNNolte IMTsai MYJensen RACaulfield MJUllum HWickremasinghe ARPreuss MScott RAWang YXGjesing APQi LGordon-Larsen PWatanabe RMVosa UQi QMunroe PBSchwarz PWong ASmith AVReilly DFCorbin LJBanasik KChai XVogel MRaffel LJGayan JTaylor KDRidker PMHong JHeianza YJames PSDedoussis GBonnycastle LLvan Dam RMSmith BHNag AKuusisto JKandeel FRMooijaart SRostgaard KÞorsteinsdottir UKeinanen-Kiukaanniemi SMKoistinen HAVacca MHerder CMohlke KLParker SCJDupuis JChatterjee KDu SSlagboom PEHsieh CHBurden FWilson JFSorensen EFeenstra BMarzi CTremoli EKuh DProkopenko IZafarmand MHSchneiderman NUusitupa MMagi RKentistou KAChen JRybin DKaspersen KJarvelin MRLawlor DALiu CTWarner JAshford SEHuo SSchoenmakers NMarz WLiu JVidal-Puig Avan Hylckama Vlieg AKivimaki MPadmanabhan SLiu SLind LJacobsen RLSennblad BHsueh WAKatie Chan KHHindhede LStringham HMPedersen OLouie TSnieder HLauzon MKuulasmaa THansen TDelgado GEGrimsgaard SSmall KSLauner LJMontasser MELai SFroguel PLeander KHoffman GJFlorez JCBertoni AGuo XHartman CARosendaal FRMarenne GNelson SCStorry JRChasman DIWarren HRStewart IDFrayling TMRay DDehghan AAn PGeller FFarrow SGigante BBluher MMagnusson PKEChalmer MANoordam RRyan KDidriksen MLaakso MBergmann SDBDS Genetic ConsortiumKalyani RRYanek LRErikstrup CSparso TNissen IVrijkotte TGMBeekman MRueedi RHan SWu JYAzzu VMori TAChitrala KNWareham NJMoslemi CSoutham LElmstahl SKaplan RRobertson NRLouloudis IHeckbert SRNelis MBlack CSchwinn MBecker DMScott LJBruun MTGrarup NWang CAPalmer CNAKaakinen MALyssenko VWilsgaard TChu AYSpracklen CNRohde RChai JFLeong AIgase MBurling KLundgaard AYao JBarroso IPorteous DJVirtue SGao YLange LATuomilehto JHwang MYKutalik Zvan der Most PJWilson PWIngelsson Ede Geus EJCFuchsberger CHorta BLTabara YGleadall NSCho KSun YVMAGICPramstaller PPMikkelsen CKiess WLin SYThuesen Bvan der Harst PBoldsen JKKovacs PRudan IShu XOXiang AHVitart VKogelman LDowsett JChambers JCCade BEFranberg MNadler JLWaage JJonas JBvan Heemst DAviles-Santa LNorth KEKumari MPsaty BMNoce DKardia SLRBurtt NPBottinger EPJukema JWLin XLuan JVangipurapu JKaleebu PCanouil MAstle WJBaldassarre DBidault GHui QNjolstad IOrd JHe JReiner AHuerta-Chagoya ALorenzo CWatkins HBrodersen TRohde PDLangefeld CDHorup Larsen MASandhu MZeggini EJensen BANorris JMCollins FSBurgdorf KMatsubara TGiulianini FAstrup ASaxena RZhao WRivideneira FWatson LPEvan den Akker EKatsuya TBohm BOSever PLoos RJFNyegaard MWagenknecht LEKwa JETimpson NJEiriksdottir GSelvin ELemaitre RNNadkarni GNBoutin TSNakatochi MBay JBisgaard HHjalgrim HLoh MBoehnke MVestergaard HYengo LVollenweider PWestergaard DKjerulff BDPeters AGrallert HRotter JIRich SSSanna SPennell CEHai YNdungu ADinh KMSetoh KOlsson MLBiggs GSabanayagam CTakeuchi FAhluwalia TSLi HMoon SFrontini MWillemsen GChiu YFChen CHKim BJLi MGoodarzi MORieneck KDziegiel MHRenhstrom KCai QIchihara SChen BHStanton ASchraut KEFerrannini ESusanMangino MOhyagi YTome ARJohnson WCThorner LWMorris APHottenga JJKooner JSEngmann JMetspalu ARaven DBuchanan TAChang YCClaringbould AZhang WAppel EVRMingrone GPiper JZhang XLigthart SBergman RNTusie TTrompet SJanaka de Silva HMcCarthy MILindgren CProvince MAKooner IKGudnason VBielak LFTai ESStefanucci LMahajan AHansen TFLee NRRaffield LIkram MAUitterlinden AMook-Kanamori DOOldehinkel AJAparicio HJO'Connell JRBonnelykke KCucca FHayward CBayraktar OAVarshney ACabrera CPZheng WRaulerson CKRedline SSorensen TIAOng KKVuckovic DRauramaa RFranks PWWheeler EAmin NBakker SJLFatumo SAMeigs JBCorrea ASteves CJSattar NLi-Gao ROuwehand WHRasmussen-Torvik LJKhor CCGoel ASaramies JBoomsma DINabika TDemirkan ATeslovich TMAguilar-Salinas CAPalmer NDOstrowski SRYokota MMoreno-Macias HHuang THuang WHenriksen APChang LCPedersen OBGong JHShi JBeilin LJHicks AALakka TAStefansson KKolcic IWang CWu PWillems van Dijk KAbecasis GRBoerwinkle EStefansson HWang HWen WBarker PSun LWang NZonderman ABStumvoll MIda Chen YDGloyn ALPistis GWood ARFerrucci LSpector TDWang TGustafsson SStrawbridge RJWang YJorgensen MEJoshi PKWu YXie TJemec GGudbjartsson DHeikkinen JTan JCheng CYEvans MKWong TYArzumanyan ZRoll KBrody JAHorikoshi MHamsten APeyser PAAdair LSLinneberg APolasek OLong JAlarcon-Riquelme MEAnasanti MDFarmaki AEvan Duijn CKim YJKato NSofer TWerge TKorner AWei WBHartwig FPDuan QSim XLangenberg CCampbell HTimmers PRHJWillems SMCampbell ALall KLindstrom JLam KfalseSMIM1 absence is associated with reduced energy expenditure and excess weight.<h4>Background</h4>Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.<h4>Methods</h4>We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-o2024-01-01T00:00:00Z2024 Sep2026-04-18T03:18:19.614Z2025-04-04T00:29:44.335ZS-EPMC76173893890614110.1016/j.medj.2024.05.015