Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight

Jessica Tyrrell, Rebecca C Richmond, Tom M Palmer, Bjarke Feenstra, Janani Rangarajan, Sarah Metrusky, Alana Cavadino, Lavinia Paternoster, Loren L Armstrong, N M G De Silva, Andrew R Wood, Momoko Horikoshi, Frank Geller, Ronnie Myhre, Jonathan P Bradfield, Eskil Kreiner-Møller, Ville Huikari, Jodie N Painter, Jouke Jan Hottenga, Catherine AllardDiane J Berry, Luigi Bouchard, Shikta Das, David M Evans, Hakon Hakonarson, M Geoffrey Hayes, Jani Heikkinen, Albert Hofman, Bridget A Knight, Penelope A Lind, Mark I McCarthy, George McMahon, Sarah E Medland, Mads Melbye, Andrew P Morris, Michael Nodzenski, Christoph Reichetzeder, Susan M Ring, Sylvain Sebed, Verena Sengpiel, Thorkild I A Sorensen, Gonneke Willemsen, Eco J C de Geus, Nicholas G Martin, Tim D Spector, Christine Power, Marjo-Riitta Järvelin, Hans Bisgaard, Struan F A Grant, Ellen Aagaard Nohr, VW Jaddoe, Bo Jacobsson, Jeffrey C Murray, Berthold Hocher, Andrew T Hattersley, Denise M Scholtens, George Davey Smith, Marie-France Hivert, Janine F Felix, Elina Hyppönen, William L. Lowe, Timothy M Frayling, Debbie A Lawlor, Rachel M Freathy

Research output: Contribution to journalArticle (Academic Journal)

108 Citations (Scopus)
352 Downloads (Pure)

Abstract

Importance
Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.

Objective
To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.

Design, Setting, and Participants
Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30 487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.

Exposures
Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.

Main Outcome and Measure
Offspring birth weight from 18 studies.

Results
Among the 30 487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 × 10−14) and −4 g (95% CI, −6 to −2g) per SBP-raising allele (P = 1×10−5), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, −394 to −21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.

Conclusions and Relevance
In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
Original languageEnglish
Pages (from-to)1129-1140
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume315
Issue number11
DOIs
Publication statusPublished - 15 Mar 2016

Fingerprint Dive into the research topics of 'Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight'. Together they form a unique fingerprint.

  • Projects

    MRC UoB UNITE Unit - Programme 5

    Lawlor, D. A. & Lawlor, D. A.

    1/06/1331/03/18

    Project: Research

    MRC UoB UNITE Unit - Programme 1

    Davey Smith, G.

    1/06/1331/03/18

    Project: Research

    MRC UoB UNITE Unit - programme 3

    Timpson, N. J. & Timpson, N. J.

    1/06/1331/03/18

    Project: Research

    Cite this

    Tyrrell, J., Richmond, R. C., Palmer, T. M., Feenstra, B., Rangarajan, J., Metrusky, S., Cavadino, A., Paternoster, L., Armstrong, L. L., De Silva, N. M. G., Wood, A. R., Horikoshi, M., Geller, F., Myhre, R., Bradfield, J. P., Kreiner-Møller, E., Huikari, V., Painter, J. N., Hottenga, J. J., ... Freathy, R. M. (2016). Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight. JAMA - Journal of the American Medical Association, 315(11), 1129-1140. https://doi.org/10.1001/jama.2016.1975