TY - JOUR

T1 - Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood

AU - Zheng, Yan

AU - Huang, Tao

AU - Wang, Tiange

AU - Mei, Zhendong

AU - Sun, Zhonghan

AU - Zhang, Tao

AU - Ellervik, Christina

AU - Chai, Jin-Fang

AU - Sim, Xueling

AU - van Dam, Rob M

AU - Tai, E-Shyong

AU - Koh, Woon-Puay

AU - Dorajoo, Rajkumar

AU - Saw, Seang-Mei

AU - Sabanayagam, Charumathi

AU - Wong, Tien Yin

AU - Gupta, Preeti

AU - Rossing, Peter

AU - Ahluwalia, Tarunveer S

AU - Vinding, Rebecca K

AU - Bisgaard, Hans

AU - Bønnelykke, Klaus

AU - Wang, Yujie

AU - Graff, Mariaelisa

AU - Voortman, Trudy

AU - van Rooij, Frank J A

AU - Hofman, Albert

AU - van Heemst, Diana

AU - Noordam, Raymond

AU - Estampador, Angela C

AU - Varga, Tibor V.

AU - Enzenbach, Cornelia

AU - Scholz, Markus

AU - Thiery, Joachim

AU - Burkhardt, Ralph

AU - Orho-Melander, Marju

AU - Schulz, Christina-Alexandra

AU - Ericson, Ulrika

AU - Sonestedt, Emily

AU - Kubo, Michiaki

AU - Akiyama, Masato

AU - Zhou, Ang

AU - Kilpeläinen, Tuomas O

AU - Hansen, Torben

AU - Kleber, Marcus E

AU - Delgado, Graciela

AU - McCarthy, Mark

AU - Lemaitre, Rozenn N

AU - Felix, Janine F

AU - Jaddoe, Vincent W V

AU - Wu, Ying

AU - Mohlke, Karen L

AU - Lehtimäki, Terho

AU - Wang, Carol A

AU - Pennell, Craig E

AU - Schunkert, Heribert

AU - Kessler, Thorsten

AU - Zeng, Lingyao

AU - Willenborg, Christina

AU - Peters, Annette

AU - Lieb, Wolfgang

AU - Grote, Veit

AU - Rzehak, Peter

AU - Koletzko, Berthold

AU - Erdmann, Jeanette

AU - Munz, Matthias

AU - Wu, Tangchun

AU - He, Meian

AU - Yu, Caizheng

AU - Lecoeur, Cécile

AU - Froguel, Philippe

AU - Corella, Dolores

AU - Moreno, Luis A

AU - Lai, Chao-Qiang

AU - Pitkänen, Niina

AU - Boreham, Colin A

AU - Ridker, Paul M

AU - Rosendaal, Frits R

AU - de Mutsert, Renée

AU - Power, Chris

AU - Paternoster, Lavinia

AU - Sørensen, Thorkild I A

AU - Tjønneland, Anne

AU - Overvad, Kim

AU - Djousse, Luc

AU - Rivadeneira, Fernando

AU - Lee, Nanette R

AU - Raitakari, Olli T

AU - Kähönen, Mika

AU - Viikari, Jorma

AU - Langhendries, Jean-Paul

AU - Escribano, Joaquin

AU - Verduci, Elvira

AU - Dedoussis, George

AU - König, Inke

AU - Balkau, Beverley

AU - Coltell, Oscar

AU - Dallongeville, Jean

AU - Meirhaeghe, Aline

AU - Amouyel, Philippe

AU - Gottrand, Frédéric

AU - Pahkala, Katja

AU - Niinikoski, Harri

AU - Hyppönen, Elina

AU - März, Winfried

AU - Mackey, David A

AU - Gruszfeld, Dariusz

AU - Tucker, Katherine L

AU - Fumeron, Frédéric

AU - Estruch, Ramon

AU - Ordovas, Jose M

AU - Arnett, Donna K

AU - Mook-Kanamori, Dennis O

AU - Mozaffarian, Dariush

AU - Psaty, Bruce M

AU - North, Kari E

AU - Chasman, Daniel I

AU - Qi, Lu

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1007/s10654-020-00638-z

DO - 10.1007/s10654-020-00638-z

M3 - Journal article

C2 - 32383070

VL - 35

SP - 685

EP - 697

JO - European Journal of Epidemiology

JF - European Journal of Epidemiology

SN - 0393-2990

ER -