Genetic evidence for causal relationships between maternal obesity-related traits and birth weight

Tyrrell, Jessica, Richmond, Rebecca C., Palmer, Tom M., Feenstra, Bjarke, Rangarajan, Janani, Metrustry, Sarah, Cavadino, Alana, Paternoster, Lavinia, Armstrong, Loren L., De Silva, N. Maneka G., Wood, Andrew R., Horikoshi, Momoko, Geller, Frank, Myhre, Ronny, Bradfield, Jonathan P., Kreiner-Moller, Eskil, Huikari, Ville, Painter, Jodie N., Hottenga, Jouke-Jan, Allard, Catherine, Berry, Diane J., Bouchard, Luigi, Das, Shikta, Evans, David M., Hakonarson, Hakon, Hayes, M. Geoffrey, Heikkinen, Jani, Hofman, Albert, Knight, Bridget, Lind, Penelope A., McCarthy, Mark I., McMahon, George, Medland, Sarah E., Melbye, Mads, Morris, Andrew P., Nodzenski, Michael, Reichetzeder, Christoph, Ring, Susan M., Sebert, Sylvain, Sengpiel, Verena, Sorensen, Thorkild I. A., Willemsen, Gonneke, de Geus, Eco J. C., Martin, Nicholas G., Spector, Tim D., Power, Christine, Jarvelin, Marjo-Riitta, Bisgaard, Hans, Grant, Struan F. A., Nohr, Ellen A., Jaddoe, Vincent W., Jacobsson, Bo, Murray, Jeffrey C., Hocher, Berthold, Hattersley, Andrew T., Scholtens, Denise M., Smith, George Davey, Hivert, Marie-France, Felix, Janine F., Hypponen, Elina, Lowe, William L., Jr., Frayling, Timothy M., Lawlor, Debbie A. and Freathy, Rachel M. (2016) Genetic evidence for causal relationships between maternal obesity-related traits and birth weight. Journal of the American Medical Association, 315 11: 1129-1140. doi:10.1001/jama.2016.1975

Author Tyrrell, Jessica
Richmond, Rebecca C.
Palmer, Tom M.
Feenstra, Bjarke
Rangarajan, Janani
Metrustry, Sarah
Cavadino, Alana
Paternoster, Lavinia
Armstrong, Loren L.
De Silva, N. Maneka G.
Wood, Andrew R.
Horikoshi, Momoko
Geller, Frank
Myhre, Ronny
Bradfield, Jonathan P.
Kreiner-Moller, Eskil
Huikari, Ville
Painter, Jodie N.
Hottenga, Jouke-Jan
Allard, Catherine
Berry, Diane J.
Bouchard, Luigi
Das, Shikta
Evans, David M.
Hakonarson, Hakon
Hayes, M. Geoffrey
Heikkinen, Jani
Hofman, Albert
Knight, Bridget
Lind, Penelope A.
McCarthy, Mark I.
McMahon, George
Medland, Sarah E.
Melbye, Mads
Morris, Andrew P.
Nodzenski, Michael
Reichetzeder, Christoph
Ring, Susan M.
Sebert, Sylvain
Sengpiel, Verena
Sorensen, Thorkild I. A.
Willemsen, Gonneke
de Geus, Eco J. C.
Martin, Nicholas G.
Spector, Tim D.
Power, Christine
Jarvelin, Marjo-Riitta
Bisgaard, Hans
Grant, Struan F. A.
Nohr, Ellen A.
Jaddoe, Vincent W.
Jacobsson, Bo
Murray, Jeffrey C.
Hocher, Berthold
Hattersley, Andrew T.
Scholtens, Denise M.
Smith, George Davey
Hivert, Marie-France
Felix, Janine F.
Hypponen, Elina
Lowe, William L., Jr.
Frayling, Timothy M.
Lawlor, Debbie A.
Freathy, Rachel M.
Title Genetic evidence for causal relationships between maternal obesity-related traits and birth weight
Journal name Journal of the American Medical Association   Check publisher's open access policy
ISSN 1538-3598
Publication date 2016-03-15
Sub-type Article (original research)
DOI 10.1001/jama.2016.1975
Open Access Status Not yet assessed
Volume 315
Issue 11
Start page 1129
End page 1140
Total pages 12
Place of publication Chicago, IL, United States
Publisher American Medical Association
Language eng
Formatted 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 birthweight 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 ( ≈ 7.2mg/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 ( ≈ 10mmHg) 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 45 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 43 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 24 Apr 2016, 10:18:16 EST by System User on behalf of Learning and Research Services (UQ Library)