06209nas a2201549 4500008004100000022001400041245014600055210006900201260001300270300001200283490000700295520185100302100001502153700001502168700001702183700001802200700001802218700001502236700002402251700001902275700001702294700002002311700001802331700001902349700002202368700001902390700002802409700002002437700001802457700001902475700002802494700002402522700001902546700002302565700001602588700002202604700002002626700002602646700001902672700002202691700002102713700002602734700002002760700002402780700001902804700002002823700002102843700002502864700003202889700002002921700002102941700001902962700002002981700001403001700002803015700001903043700002203062700002203084700001903106700002403125700002103149700002503170700001303195700002103208700002203229700001903251700002203270700002403292700002203316700001803338700002603356700002003382700001903402700001603421700001803437700002303455700002203478700001903500700001703519700001403536700001703550700002103567700002203588700002103610700002003631700002003651700002103671700002203692700002003714700002403734700002303758700001703781700002503798700002903823700002203852700001703874700001803891700002603909700002003935700002303955700002003978700001903998700002804017700002304045700002004068700002204088700001704110700002104127700001904148700002404167700002204191700002204213700002504235700001904260700002204279700002104301700002004322700002104342700002304363700002504386700002404411700001904435700002104454700002104475700002904496700002504525700002004550700001904570700002304589700001104612856003604623 2020 eng d a1573-728400aMendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.0 aMendelian randomization analysis does not support causal associa c2020 Jul a685-6970 v353 a
Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (β = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (β = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (β = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.
1 aZheng, Yan1 aHuang, Tao1 aWang, Tiange1 aMei, Zhendong1 aSun, Zhonghan1 aZhang, Tao1 aEllervik, Christina1 aChai, Jin-Fang1 aSim, Xueling1 avan Dam, Rob, M1 aTai, E-Shyong1 aKoh, Woon-Puay1 aDorajoo, Rajkumar1 aSaw, Seang-Mei1 aSabanayagam, Charumathi1 aWong, Tien, Yin1 aGupta, Preeti1 aRossing, Peter1 aAhluwalia, Tarunveer, S1 aVinding, Rebecca, K1 aBisgaard, Hans1 aBønnelykke, Klaus1 aWang, Yujie1 aGraff, Mariaelisa1 aVoortman, Trudy1 avan Rooij, Frank, J A1 aHofman, Albert1 avan Heemst, Diana1 aNoordam, Raymond1 aEstampador, Angela, C1 aVarga, Tibor, V1 aEnzenbach, Cornelia1 aScholz, Markus1 aThiery, Joachim1 aBurkhardt, Ralph1 aOrho-Melander, Marju1 aSchulz, Christina-Alexandra1 aEricson, Ulrika1 aSonestedt, Emily1 aKubo, Michiaki1 aAkiyama, Masato1 aZhou, Ang1 aKilpeläinen, Tuomas, O1 aHansen, Torben1 aKleber, Marcus, E1 aDelgado, Graciela1 aMcCarthy, Mark1 aLemaitre, Rozenn, N1 aFelix, Janine, F1 aJaddoe, Vincent, W V1 aWu, Ying1 aMohlke, Karen, L1 aLehtimäki, Terho1 aWang, Carol, A1 aPennell, Craig, E1 aSchunkert, Heribert1 aKessler, Thorsten1 aZeng, Lingyao1 aWillenborg, Christina1 aPeters, Annette1 aLieb, Wolfgang1 aGrote, Veit1 aRzehak, Peter1 aKoletzko, Berthold1 aErdmann, Jeanette1 aMunz, Matthias1 aWu, Tangchun1 aHe, Meian1 aYu, Caizheng1 aLecoeur, Cécile1 aFroguel, Philippe1 aCorella, Dolores1 aMoreno, Luis, A1 aLai, Chao-Qiang1 aPitkänen, Niina1 aBoreham, Colin, A1 aRidker, Paul, M1 aRosendaal, Frits, R1 ade Mutsert, Renée1 aPower, Chris1 aPaternoster, Lavinia1 aSørensen, Thorkild, I A1 aTjønneland, Anne1 aOvervad, Kim1 aDjoussé, Luc1 aRivadeneira, Fernando1 aLee, Nanette, R1 aRaitakari, Olli, T1 aKähönen, Mika1 aViikari, Jorma1 aLanghendries, Jean-Paul1 aEscribano, Joaquin1 aVerduci, Elvira1 aDedoussis, George1 aKönig, Inke1 aBalkau, Beverley1 aColtell, Oscar1 aDallongeville, Jean1 aMeirhaeghe, Aline1 aAmouyel, Philippe1 aGottrand, Frédéric1 aPahkala, Katja1 aNiinikoski, Harri1 aHyppönen, Elina1 aMärz, Winfried1 aMackey, David, A1 aGruszfeld, Dariusz1 aTucker, Katherine, L1 aFumeron, Frédéric1 aEstruch, Ramon1 aOrdovas, Jose, M1 aArnett, Donna, K1 aMook-Kanamori, Dennis, O1 aMozaffarian, Dariush1 aPsaty, Bruce, M1 aNorth, Kari, E1 aChasman, Daniel, I1 aQi, Lu uhttps://chs-nhlbi.org/node/8410