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Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

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@article{e6fc61412f8b4cb4b0c05754c6ce325d,
title = "Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors",
abstract = "Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.",
author = "{EGG Consortium} and Warrington, {Nicole M} and Beaumont, {Robin N} and Momoko Horikoshi and Day, {Felix R} and {\O}yvind Helgeland and Charles Laurin and Jonas Bacelis and Shouneng Peng and Ke Hao and Bjarke Feenstra and Wood, {Andrew R} and Anubha Mahajan and Jessica Tyrrell and Robertson, {Neil R} and Rayner, {N William} and Zhen Qiao and Gunn-Helen Moen and Marc Vaudel and Marsit, {Carmen J} and Jia Chen and Michael Nodzenski and Schnurr, {Theresia M} and Zafarmand, {Mohammad H} and Bradfield, {Jonathan P} and Niels Grarup and Kooijman, {Marjolein N} and Ruifang Li-Gao and Frank Geller and Ahluwalia, {Tarunveer S} and Lavinia Paternoster and Rico Rueedi and Ville Huikari and Jouke-Jan Hottenga and Leo-Pekka Lyytik{\"a}inen and Alana Cavadino and Sarah Metrustry and Cousminer, {Diana L} and Morgen, {Camilla S} and Allan Linneberg and Jakob Stokholm and Vinding, {Rebecca K} and Chawes, {Bo L} and Michaelsen, {Kim F} and Jens-Christian Holm and S{\o}rensen, {Thorkild I A} and Hans Bisgaard and Klaus B{\o}nnelykke and Torben Hansen and Charlotta Pisinger and Vaag, {Allan A}",
year = "2019",
month = "5",
doi = "10.1038/s41588-019-0403-1",
language = "English",
volume = "51",
pages = "804--814",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "5",

}

RIS

TY - JOUR

T1 - Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

AU - EGG Consortium

AU - Warrington, Nicole M

AU - Beaumont, Robin N

AU - Horikoshi, Momoko

AU - Day, Felix R

AU - Helgeland, Øyvind

AU - Laurin, Charles

AU - Bacelis, Jonas

AU - Peng, Shouneng

AU - Hao, Ke

AU - Feenstra, Bjarke

AU - Wood, Andrew R

AU - Mahajan, Anubha

AU - Tyrrell, Jessica

AU - Robertson, Neil R

AU - Rayner, N William

AU - Qiao, Zhen

AU - Moen, Gunn-Helen

AU - Vaudel, Marc

AU - Marsit, Carmen J

AU - Chen, Jia

AU - Nodzenski, Michael

AU - Schnurr, Theresia M

AU - Zafarmand, Mohammad H

AU - Bradfield, Jonathan P

AU - Grarup, Niels

AU - Kooijman, Marjolein N

AU - Li-Gao, Ruifang

AU - Geller, Frank

AU - Ahluwalia, Tarunveer S

AU - Paternoster, Lavinia

AU - Rueedi, Rico

AU - Huikari, Ville

AU - Hottenga, Jouke-Jan

AU - Lyytikäinen, Leo-Pekka

AU - Cavadino, Alana

AU - Metrustry, Sarah

AU - Cousminer, Diana L

AU - Morgen, Camilla S

AU - Linneberg, Allan

AU - Stokholm, Jakob

AU - Vinding, Rebecca K

AU - Chawes, Bo L

AU - Michaelsen, Kim F

AU - Holm, Jens-Christian

AU - Sørensen, Thorkild I A

AU - Bisgaard, Hans

AU - Bønnelykke, Klaus

AU - Hansen, Torben

AU - Pisinger, Charlotta

AU - Vaag, Allan A

PY - 2019/5

Y1 - 2019/5

N2 - Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

AB - Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

UR - http://www.scopus.com/inward/record.url?scp=85065213720&partnerID=8YFLogxK

U2 - 10.1038/s41588-019-0403-1

DO - 10.1038/s41588-019-0403-1

M3 - Journal article

VL - 51

SP - 804

EP - 814

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -

ID: 57091750