“aeThe | - polygenic - feature | of | ‘life.   i Simakes - it eee Ne RRR OD RN_ imperative | tO | Maetake | into | ) account | the | - unob- served I reso.”| hidden | : heterogeneity i yin ope eeindividual | | frailty 1 eefor t r two t ) reasons. ] . First, t , there i >is | ; unobserved heterogeneity - in. -an SE EEEindividual’s _ genetic LL LLIN FOEmake-up, which | | accounts | ett tefor | about -7B of ’ the Ne Oevariation | in| my oolife | span | _according | “ &*to | pan) previous : mea MPstudies | 8"(cid:10)@(cid:13)(cid:15) et | cal., /EE,0 _Herskind « let ; -al., /EE10 Yashin “epeeand Jachine, /EE7:(cid:30) Regarding rowerthe number of 9 AAO?genetic variations ™~ seeeethat ND RORcontribute | to | life. span,  nee ey AMartin | 8/EEJ: oe| estimated | | that | there « could | of| be up | to i ) about J...(cid:30) In such |  highly cee Rn peseene Apolygenic pe EE ND Asituation, asit xmis advisable to. consider the SE Teeinfluences from | other —e EOunobserved | ad Ped| genes” Jon; when - | making : an | inference - from | the | - observed « | ones. Second, 1 there. are also 1 EEE EN) non-genetic | factors | that | eee 8t have  | predominant | influence « on | | life : : span, % and | waneeg bee”| these « - consti- tute « SALE Ee”- another | layer ¢ - of | ' heterogeneity “FPin i LLL IE| individual | | frailty. * _ The « NEE EEE OEEexistence - of § f genetic ¢ >and 1 | non- genetic | EEE EI EOIheterogeneity in “Soeindividual - es   affecting   span | | Can | NN eeinfluence’ an inference Gee“ refrom ; . an SEN OO| observed | eee yee| genetic | EN NINE OI IIE- polymorphism. | In | OUL 5 DEED ARR SFE‘analysis, 2(cid:15) also | ) tried | | to ) apply al | simple model { | that « does 1 not | take | ~ peewee bees’‘unobserved | | frailty | into ; EN PII) account. ' The - estimated | sw “MPR? ™relative 1 a eeerisks | of gene-—sex 1 interaction { \ for 1 the three : oo OO- significant t alleles ; Were § > systematically \ / weaker t than | they were in| | the heterogeneity model | oewith | risk | parameters | .(cid:30)F71 for. NN IISangiotensinogen "-,7(cid:27) .(cid:30)F7J for | FVII (cid:25),7,  and | .(cid:30)F1. ) for | 9(cid:1)(cid:29)(cid:29)5,-,&/.(cid:30)   - differences 1  in | > eee ee| parameter | ED‘inference present ; La | | good ¢ — << eee| example of 1 * the « difficult : | situation | facing | - studies « of | eeelongevity and « | of 1 ’ multi- breefactorial ok — iediseases ee IN LLL IIIS(Clerget-Darpoux, -...:(cid:30) NEE IRE IISIndividual ENE EEE OOheterogeneity in the unobserved attributes is an Ae oeobstacle that spss ameprevents us from unraveling ounthe eee yeegenetic component in

Oeppen from Cambridge OTUniversity 9%for oOuseful discussions. The authors also want to NPPthank the DI III III IID!anonymous ON MEE ENreviewers for their very valuable suggestions that helped in improving | the 1 ween J eetext.

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