Type 2 diabetes develops from the interaction between non-genetic (environmental/lifestyle) and genetic factors. One of the challenges of personalized genomics is the prediction of disease risk. This review examines the challenges of risk prediction studies and the barriers to their implementation in the clinicpeer-reviewe

Pace, Nikolai Paul

OAR@UM

MINI RfVlEW IS THERE A ROLE FOR GENETIC RISK PREDICTION STUDIES IN TYPE 2 DIABETES? """" l'frt1 .I ...... " dtttIofd from tbt inlnXtioo ~ 1I00I . (lC'Mic (mvil'("",,,,,ullliltily\t) and (lC'Mic fiK1On. One '" ,ho d>altmp '" pman.oIitN srnoma is tl>t pmliclion of do.m. riot. 1his mirwenm"'" 'ho~ofrilJ<.pmlic"on .. udic> and ,ho b.vritn 10 ,h./i, imJ'lnntn!a!ion in tl>t dinic. moocn~ lho .. "tlie OIudy of CQIl'Imon oomplrx di,..", h •• undrrgon •• ", ... 1, .. lran.fo,m.'i"" fullm"ing Ih. I, .. ."h of .. .,,,,,, • • wld< ... ",i>lion K'>n> (GWAS). It..,.. ho, .. i,ully mhan<"" "",r know""'" "" Ih. ,,,,,nib.,,,,,,, of 'om""", grntIk ,..,laIion In mul'if.oc,,,,,ill Ji..,..... Fu"h.rnnort. lho (<>ti .nd lim<frmon ~ for wbolo gmom< ~'" h;u «>nIUlr.ltd 10 dlmlnioh. 1h<rtbf, 'M ondo:;nw of mI, ... J'I'OfI'" h;u now "'ifiN from bnnc 'M sol< ...aIm 01 illlnNilonal <Oft$OIIio 10 lying wilhin lho technieal ~~'Y and ~ ror.><ttainI< ofindmctual acad<mi<: and ...w.1Ch i .... "ullOllt.. fIIlM lAIIlRArOIIY IENCI TD IllNICAI. CARE U ..... niobly. ,ho groom.,. ...... utioo ha.\tod 10 lho idtnllfica,ion ofll"rnho;J. ofloci ,h ... rt ."""i .. td wilh dlnical ph.n<>ll1'" or Ji,...,.. ;1Otts. Y<1. ,n. 'btr><h 10 bNJidi l ... n,I.,1on from .. nrunic Ji"""r.'1)' 10 dinic.1 pr><'ie. i. on obKurt .nd oft." (<>n,rr.)\...,.w fitl.! ,hal "" ..... nlS I maj<>r ,NU.n .. ,o physiciall$ and rt$rar<h<n oJr.l:t. Many ",know""", 'NI ""h • '",ru-irioon ~""' • ,"""Iks", .toi~ In pModlgm from lho 1,...j;,ionaIM."ddian B""'iC$ ~h. AJ ,ho .j")I ...... bIoIosY If'I"'*h 10 cornpIn .I ....... bKomn mort .... a1to out wrdtnunJing oflownarr phlWiosr.1I It ~ ,Iw ,ho conrnbullOll of .. "&It genes comidtrtd in boIaIlon is rtLarn-rly ml""'. INoI<Id tptgc-n<lic. Jm<'~ and ~ .",ironmtnl In'rroctioo. crilically undnl ... ho tli<>Iofy and I"'I~ of multifa.:tonoJ di ......... Con''''''ingly. Ind .... rW vtTt'utfl h""lpI'Ung up 'h>! mw u .. of gtoomic do .. '0 I""""id< risk pmlic,lon Informa.ion '0 indi"id .. ,!. abou, hul.n. Ji .. ,,.. .nd .... n bth .. inr>II ... ,IS, Co",!",n;" !iu ll.ndM. (www.2J.nd nlo.(om )d.rlnglydaimlhar "21ondM.tan NlIDlAI P PAIl h.tp)'OU diKm..,.IkM")'OU' ....... may al'l"t<, you. do.anceo of d.--.Iopng ,"2rioar.u .I ........ ond cond~""", .. wdl .. ,,,,, .. sud> I • .,hktk obiI~y", Sr.><h bold and ....... nlhu.iulic pmlklicJ<ls "",ding po:nonoliml mrdidn< """"''' "i!h !iIoo< '" gtoom. ...... rtll<n ,nd m..-i, c.rtful $Crullny'. RISK PREOlmON MODELS IN rm 2 OI.l.S£rn li1>t 2 di,be ... ",.11o.u. (nml) II • ,ommon n,ul!ifaclori.1 diM>", caU<Od by 'M """pi .. '''ltrplay btl.....," i<ntli<.nd lIOOI.gtntI;': ( .... 'ironmtn .. UI'fhtyIt) fact<m. III> highly ;,.,;!>bIt. with In. rtbli,,, rUIr. lor lho .1",,_ in IndMcl..u. ""'" a family hilolOfy bring 1..-0- 10 .... ·fuId hishor ""''I''rtd 10 indmd ..... ...,!bout a famdy h"'oryofTlDM', A. a nwnb<-r al ~:U _ loci ha>" t..en 1U(>(i.oI..! ..-iIlI TlD~I. im'«lip"" IY ... """" ........ wh<1htr <o",b",,,,..,.., of rilJ<. aDdr< Qn be ustd 10 «>notru<l .. ntloe riok JCQrt$ lor "" rar!i..-id...,,,fiation of ind,\"iduai. ill risk. CUNICoIlIm PAEIIETlON De>pil •• ,·ido",. ,h.;,t .arly hf«I),1t or phormacologJ<o.i ino." ..... ,ion' <:In p,,,, .. n' "" dd,y .h. devtl"",nem .,r ,h. d',... .... n. pmlk'ion of rI..,.,f ","w·onrtl nll.\! II "'" P"" of roo,in. dinko.l J'TK!i« '. 1Wu ,u'rtnlly ., .. ilmlt risk prr;liclion $C",,", art bo...,j "" dcmov.pItk", OII,hropomtlric and b;oc:hmrical dou.. 1"" Coml:oriolso' TlIl~1 ru.k $Con" i. bo...,j on •• ...,.xr. family h, .. ory. 8.\1\ .nd omotIns ........ -...d lilt Framingham oIf>pring TlD~1 ri>k K(U' I",,,, I .... ,.. boling blood gIua>st and (;pid pro/ilt I"'rarntIffllnl" ru.k nInoIiIIlon. , .... ,_ rUIr. prr;liclioo oJscrriIhlN pro>id< ............... mtaow-t of dioaimillllioo ofinr.:idm, ~ ofnl)~I. with ana ou>dtr ,II< <u''''' (AUq Yaltits of 0.75 and 0.a51"t1f'«1'vdy. FurtMr-rnou. tl>t addilion '" non ' '''''"rdy mt>.$ur..! indicts of Jiuc",," m<I"wi<m •• uch .. f'''ln8 pWma insulin. trom.-cr.laOi. model .,,,,,,,,,,,,, ·«lIm,!td In.ulln rt>i".nc:. (HOMA·IR) and • Iwo hou, 0<11 gl",_ lol .... n« !til. don "'" impro .... T2D~! ,isk prt<iic.ion'. Ii{ IT'Ih~ AI i ',!' ~ J I, . MA IllIS or OI!itASl R1S~ Gtl\01ypn ... '1'I".liog'$ dl",_ biorn.rJuo" .... !hey do nOl ,lIon8" with ond .... lndtllCruknl of .go. Ttdlnologic.>l ""'-....c .. conlin ... to Imr~ "" goDllfJ-p;ng offi&ney.nd Ih""'shp\ll .nd oK ... IMobiIlty II> muhipln singlt n ... lcc!ide poIymo<phl"" (SSP) UNt' in oomb"ulion wilh h~ IidtIlty. GC1IOIypo. ""'0' tIw inlngwng ~ "' .. dttmnlrution from Y"""8'" groups. ~. in 1M lisIM '" MioI."UCUIIr difait pr<"V<nllon. .... itT InlOf>'<'Mion has 1Il00 rrwtlmum btnt6cW 011«.., WI£Jt IllS( PIIDItIIIII 'M IolnIh~(.Ilion of gt'fIO\yJICS III>! conftr riok In TlOM and lhoi, II'I("'por'lion InlO robu>tly ",Ud.utd riok·oronng • lgorIthml b.wd I)fI phmol)pt has long bNn ,,,,,jkltrtd .s tho '!JoIy (;,.il" o(TlllM gonttles. Rol't ll'dy ftw .tuditl ... W th .. Inmll!!.". lho al'rlka1ion 0( gtnoti<: risk """'" in prtdi<:t ing TlDM, tit"'" a. CIlot·conlroi or longitudinal fullow·up ltudieo.. In .U """iel. IrrtSp«I"" oft.:...· l'I'WIy. or ..... ich rill< loa " ..... """,io,krtd,.nd Itmp«tn .. ", ... htth.a- gtnrtic """'" " ..... """"ltd '" nol. 1Iw .. 1itnt ~ it , .... indivi<luol. with _ .. 11Itb ........ 1II ,..nm-.. ttw. I~ wnh ,.,...,. n.k alIdn. Hn"ft1 tf '" dn-dopod. gmtti< ri>I:; KOf't .... "'}.j TlOM·wocbltd loci In ....... l.80(llndi>i<huls from dltf ...... tfhnle bxkground< ''In'Kntllivt of lho US I"'I"'wion·. In. Ihlft.ynr foIlow-,,!, ifudr. 'her demon>t~td th .. hlghn ",Jut, "a "'fishkd 8"n.,,( n.k ""'" ....... """,;'Itd with Il'I(rnstd ,iok of pt"l!m&ion ' 0 TlO.\1. 1h.: >tudr .Iso rtporttd th .. In Indlvldu.l. wI!h high gtnttle ,Ilk >COrn, inlon,i,.. IIf .. !yk Inl",..n!I\lfI ""'I .llo(lOltd wl!h higho, Inckl<nc<" "lrtl'H)n !o oor.na1 g1ucoso "lul.otion. On 111< othor h.nd Mdp tf a! inV<\1Ig>!td. g<r1tti<: >COlT hastd on tS TlO,,"I-uso<i;lt<d 10<'1 In OWl" 2.000 indhidu.11 fr"", Iho I ''''mln~h'm Otf.ptlnl Study whkh we", foll.,..·td (<>r tw~ltty·~lgttt )'t .... 'Mr «port !h.1 gfntti<: n.k >Cor .. prtdic!td now co ... ofT2IlM. wllh • 1 ~ I~in r<1.ati, ... riok"'dl ..... " .. ri"'oIldr~. W..tdon d aJ rtporttd .,milo, findings u,lng an un .... igflltd 8" .... ic oco« con>tructtd from jllOI j conlmort ltlgItIy'ur!iao.,J ""Wlts ". SlmiLufy, L,.....ko d aJ rtpOf1td OIl gt'Mic" """"" .... '" 16 nl)M·......u.ltd loci". In" 01 w.. and OII~ >t..dieo, u.. rnuIts ~ 1ha! """bittlhO'U 01 risk ...... an bot uK<! 10 idmIifr. gndictt! 01 KftI<Iic risk lhalilu. btu .. pmli<:Iil .. ~iIy dun singlt po/ymorpItllms CORIidtmI In lsoIal""'. o..pifC" lhe nlablishtd ......... "'" bttw<mIM numbtt " ,,,,,;'nt. and di ...... rill:. gmttic fill< 1(0<eI tn i!.oIOlion otr.. poort. disc,lmin.lory ca~l!y (AUC of(l,SS !o 0.68) "'htn oon'p.rtd !o dini<::ll rill< J""tdichOn .Igorl!hm.". Inl<, .. tingly . !he JI",imin.lory capacl!y of il"ntti<: ri'" 1(0 .... don nO! rorrtl.to with 1M numbrr of~~Ps Includtd In !nO rilk "or~. 111< hlght<t AUC (0.68) ,,,,I ... ".1 I'C'f"OI'ttd In IIw IIoInilstudy til>! <"",io,k~ I t S~PS In • proIp«1l"" .I""r .x.lgn". and !M ~ AUC nlur (0.55) rtpOI1td In lho FIM)RtSC ltudy III.llutd thr tam< II s,\'Ps and.., add~1OnaI 8 polymorph""", tit • ootf-KCt...w study daI", ". lh.: .......... publioht-d n.k J'«<Ioct_ >tud;., also dilf .. in 1M gtn<Ilc nrIInlt ~ In ..... , ri>k rnodeb. Sineo ~. diKovfty. tIw Jr<" ....,.,nty of <Iud;., Iu,.. indOOtd TCF1U tit IIw II>! of rill<·conr.m", ........... 1hio ..... 1w betn ludtd >t 0 .... 0( tho tNge>t "',,<so .. orin ofnOM gor>ttia~. as rom""", ."riants In Ihl. go .... Iu, ... ma,ktd .nd .. producible di"«to on JI", ... ,ill:. SI",o iii Inilial di""""1' by til< dtCOm: In",>!ig>I<>rlln 2006 in on leob nd ic popu;'!ion " .lht roIt ofTCF7l.l tn T2D~1 ,i.k h .. betn ",,,Hcattd In I"triou> eo .. "",,"" anJ 00/1 ·&'"",,0" rohom". ,11< majon1y "'inV<$!lgaoH)n, h ..... also incllldtd -:< MITFORMIN INO INTENSIVE LIFESTYlE INTERVENTION WAS EFFECTIVE RISK OF O~BETES INCIDENCE IT ANY LEVEL OF GENETIC RISK gtntlic ,,,,,ianlS In Sl.CJOA8. IGF2BP2. PPAR_gam." and KG ... ) II. Mo.t of thot 0100 SNI'> = ind..&d in on" '" two modds only. <0 W« i< cortikkrabk htttrogrnrily in tht <D<ting gtoeHe ri$k mad ... f.". TID.\t. GOIrn: RISK SCIIAES - WllUUJ TlI£Y IIIAIIAIIFHRW'I? NOIwilh>1aoo",! tho aademk isM...,.. in !l'""elk risk !WI'O, lhtir poIm1lo1llramU.liOll<ll dinO! 'lpplkation in rilJ< prediction .. nui", to be d".rmined.l'rosp«;1i," "0><1..,....,,, dcmminod th. llt.. commonly mtaWrM dink.1 ,hI< facIor. uTID.\! ... p<:rWmuJ harbingers ofT2D~1 risk. 1 ... addition of F""f)~ dal. 10 lhesoo risk factors II,,, .. od<ltJ little uod'ul inlorm.lion '0 riol; prediction in porublions.t r;>k. Phm.,!}"pic fill: bctors, in p.oniallar obesity and wipooily indicts, ~ .. ith ramilyhistoryofTID.\j .... <i •• iroaptn,jvt UldnWy mtUIIrN clinical risk factors thai .,.., sup<rior to .ny prn<n~y ~ .... gtn<lic ri$k f><t<lr:l in di ...... pm:!iction. Trtalmtnl ... 'ith mttfonnin .M inltruiI-.c lifnrylr iDkn'<l\lion was dJ«m" at rNucing tht risk of diabd« ~ at any Ind of I""'ic rUk', In 'l""'f""CIivt invntJg.tioon that c~<d '" 2!J.. .. 1dt gent1ic rut. oc«< 1<> II>< CambridV.nd fruninpam TID;\[ rill< $<<>rtS, Talmud tI aJ «>nocIud..:I thai 'he odd~ion 01 ~l'" dn. I" ~notYI"'·ba$<d ri$k IDI><kb did "'" i"""", .. d;,.;nminalj"" boIWfttI nDM ~:and rontrols'. Sim~arly. ,t.. ="'" CARDIA "..d)o (Coronary Art<ry Ri,k De .. Iop".,n. on Youog AJul,,) condudod .hOl ~".. KO<e don ...,. i"'f"'>'"" predktiort "'".,. rou.ine dinical .......... m.n"». THE WAY FORWARD A numbc-r of rcqu;....,.n" mu~ be NlfillnJ for TID.'1 gmotic rio!; pRdktiort in order for ~ '0 >UCCaSfully ..,h~,M bmcIt to bN,ido .ransition: :< -Qinica! modd. rorn~ to tho o~islj"g cardiov.scular ril.k """'" must bo.,-aibtlIo '0 suklo Irnlnxn' ~ifl'l<S. Foe- aampl •. tn. o<UbIisbN F ... minghmi Cordiovascular RI<k Srom for cortI<IM)" "wt di~ n$l: ~ktion ..., ~ to guide LDL·C WgrI' In inJi,iduol potl<,," ~ 011 tn.;r • ...,·ynr ..... of d .... sr'J; EJ~<onsciou> hnI.h car ... rvk .. obo «qUi .. ~-ping to bo camed OUt within rnsonobIo <O"Hr>d timofwnes: Gc-notic rio!; K<mS >Ioould bo d.,..lopod tui"1! represmtoti,.. samples oftn. populations in "'hich they wiD u~im.t<ly b< applin! to lIrge1 prt""tfI1ion; Study mtlhodologr ~'bcantly '"'paclS 011 the discriminatory capa<ityof smrtic ril.k KOR>.. I'rospoctiv<-foIIow·up studios a .. best ."ltN for gftIOIic rilJ:. prodiclion" . roN""'" QinicWI< .hould~ .. od,-ocat< ttw: main'<nan« of • hcaIthy ....-ight."d babncod d,rt a. the «Ifn<'rU""" ofT2D')'1 prn-rn.iort • irTdpoctn~ of"",,", genotyp<. _ ...... g<n<tK rUIt S<O«$ could b<' II$od to idt"tify ,ubgroup< with parti<uW-dn ... od ..... fur .. 'V'od "".,..nor ri,k modi6c:llion p~ or p/anna<och . ... py. Such I"""S"m'..., ...,..,..""·i01<",;",, . M in bNhhcafl' >j')\I'Im olfl.'(Ud by finih> rfSOO"!'$. could off..,.. p<nOOali...t al'l'fO'O'h 10 ri,k p"""",ion in .. 1«,«1 il>di'id ...... t\.,..rtltoloss til< dinK.1 irnpona~ of <,,<OS odip<>l.ily""" obesity IS tht principal fu"",ional ril.k facton in TID.\! rio!; drt •• minotiort and di ..... ~ .. mai ... undispulcd X CLINIC SPACES AVAILABLE at Valletta.. Aoriana, Hamrun & Sliema. Interested Medical Professionals contact Chemimart Head Office &nail: office@lchemknartgroup.oom w21492212 i • I • i 

Is there a role for genetic risk prediction studies in type 2 diabetes?

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Is there a role for genetic risk prediction studies in type 2 diabetes?

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