Abstract
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.
| Original language | English |
|---|---|
| Journal | European Journal of Epidemiology |
| Volume | 35 |
| Pages (from-to) | 685–697 |
| Number of pages | 13 |
| ISSN | 0393-2990 |
| DOIs | |
| Publication status | Published - 2020 |
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Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood. / Zheng, Yan; Huang, Tao; Wang, Tiange; Mei, Zhendong; Sun, Zhonghan; Zhang, Tao; Ellervik, Christina; Chai, Jin-Fang; Sim, Xueling; van Dam, Rob M; Tai, E-Shyong; Koh, Woon-Puay; Dorajoo, Rajkumar; Saw, Seang-Mei; Sabanayagam, Charumathi; Wong, Tien Yin; Gupta, Preeti; Rossing, Peter; Ahluwalia, Tarunveer S; Vinding, Rebecca K; Bisgaard, Hans; Bønnelykke, Klaus; Wang, Yujie; Graff, Mariaelisa; Voortman, Trudy; van Rooij, Frank J A; Hofman, Albert; van Heemst, Diana; Noordam, Raymond; Estampador, Angela C; Varga, Tibor V.; Enzenbach, Cornelia; Scholz, Markus; Thiery, Joachim; Burkhardt, Ralph; Orho-Melander, Marju; Schulz, Christina-Alexandra; Ericson, Ulrika; Sonestedt, Emily; Kubo, Michiaki; Akiyama, Masato; Zhou, Ang; Kilpeläinen, Tuomas O; Hansen, Torben; Kleber, Marcus E; Delgado, Graciela; McCarthy, Mark; Lemaitre, Rozenn N; Felix, Janine F; Jaddoe, Vincent W V; Wu, Ying; Mohlke, Karen L; Lehtimäki, Terho; Wang, Carol A; Pennell, Craig E; Schunkert, Heribert; Kessler, Thorsten; Zeng, Lingyao; Willenborg, Christina; Peters, Annette; Lieb, Wolfgang; Grote, Veit; Rzehak, Peter; Koletzko, Berthold; Erdmann, Jeanette; Munz, Matthias; Wu, Tangchun; He, Meian; Yu, Caizheng; Lecoeur, Cécile; Froguel, Philippe; Corella, Dolores; Moreno, Luis A; Lai, Chao-Qiang; Pitkänen, Niina; Boreham, Colin A; Ridker, Paul M; Rosendaal, Frits R; de Mutsert, Renée; Power, Chris; Paternoster, Lavinia; Sørensen, Thorkild I A; Tjønneland, Anne; Overvad, Kim; Djousse, Luc; Rivadeneira, Fernando; Lee, Nanette R; Raitakari, Olli T; Kähönen, Mika; Viikari, Jorma; Langhendries, Jean-Paul; Escribano, Joaquin; Verduci, Elvira; Dedoussis, George; König, Inke; Balkau, Beverley; Coltell, Oscar; Dallongeville, Jean; Meirhaeghe, Aline; Amouyel, Philippe; Gottrand, Frédéric; Pahkala, Katja; Niinikoski, Harri; Hyppönen, Elina; März, Winfried; Mackey, David A; Gruszfeld, Dariusz; Tucker, Katherine L; Fumeron, Frédéric; Estruch, Ramon; Ordovas, Jose M; Arnett, Donna K; Mook-Kanamori, Dennis O; Mozaffarian, Dariush; Psaty, Bruce M; North, Kari E; Chasman, Daniel I; Qi, Lu.
In: European Journal of Epidemiology, Vol. 35, 2020, p. 685–697.Research output: Contribution to journal › Journal article › Research › peer-review
}
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 -