Maternal and fetal genetic contribution to gestational weight gain

N. M. Warrington, R. Richmond, B. Fenstra, R. Myhre, R. Gaillard, L. Paternoster, C. A. Wang, R. N. Beaumont, S. Das, M. Murcia, S. J. Barton, A. Espinosa, E. Thiering, M. Atalay, N. Pitkänen, I. Ntalla, A. E. Jonsson, R. Freathy, V. Karhunen, C. M.T. TieslerC. Allard, A. Crawford, S. M. Ring, M. Melbye, P. Magnus, F. Rivadeneira, L. Skotte, T. Hansen, J. Marsh, M. Guxens, J. W. Holloway, H. Grallert, V. W.V. Jaddoe, W. L. Lowe, T. Roumeliotaki, A. T. Hattersley, V. Lindi, K. Pahkala, K. Panoutsopoulou, M. Standl, C. Flexeder, L. Bouchard, E. Aagaard Nohr, L. Santa Marina, M. Kogevinas, H. Niinikoski, G. Dedoussis, J. Heinrich, R. M. Reynolds, T. Lakka, E. Zeggini, O. T. Raitakari, L. Chatzi, H. M. Inskip, M. Bustamante, M. F. Hivert, M. R. Jarvelin, T. I.A. Sørensen, C. Pennell, J. F. Felix, B. Jacobsson, F. Geller, D. M. Evans, D. A. Lawlor*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background:Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methods:A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Results:Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10 â '8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.Conclusions:We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Original languageEnglish (US)
Pages (from-to)775-784
Number of pages10
JournalInternational Journal of Obesity
Volume42
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Weight Gain
Mothers
Body Mass Index
Genome
Birth Weight
Glucose
Type 2 Diabetes Mellitus
Pregnancy-Specific beta 1-Glycoproteins
Phenotype
Fetal Weight
Replication Origin
Gestational Diabetes
Genome-Wide Association Study
Amniotic Fluid
Fetal Development
Placenta
Blood Vessels
Fasting

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Warrington, N. M., Richmond, R., Fenstra, B., Myhre, R., Gaillard, R., Paternoster, L., ... Lawlor, D. A. (2018). Maternal and fetal genetic contribution to gestational weight gain. International Journal of Obesity, 42(4), 775-784. https://doi.org/10.1038/ijo.2017.248
Warrington, N. M. ; Richmond, R. ; Fenstra, B. ; Myhre, R. ; Gaillard, R. ; Paternoster, L. ; Wang, C. A. ; Beaumont, R. N. ; Das, S. ; Murcia, M. ; Barton, S. J. ; Espinosa, A. ; Thiering, E. ; Atalay, M. ; Pitkänen, N. ; Ntalla, I. ; Jonsson, A. E. ; Freathy, R. ; Karhunen, V. ; Tiesler, C. M.T. ; Allard, C. ; Crawford, A. ; Ring, S. M. ; Melbye, M. ; Magnus, P. ; Rivadeneira, F. ; Skotte, L. ; Hansen, T. ; Marsh, J. ; Guxens, M. ; Holloway, J. W. ; Grallert, H. ; Jaddoe, V. W.V. ; Lowe, W. L. ; Roumeliotaki, T. ; Hattersley, A. T. ; Lindi, V. ; Pahkala, K. ; Panoutsopoulou, K. ; Standl, M. ; Flexeder, C. ; Bouchard, L. ; Aagaard Nohr, E. ; Santa Marina, L. ; Kogevinas, M. ; Niinikoski, H. ; Dedoussis, G. ; Heinrich, J. ; Reynolds, R. M. ; Lakka, T. ; Zeggini, E. ; Raitakari, O. T. ; Chatzi, L. ; Inskip, H. M. ; Bustamante, M. ; Hivert, M. F. ; Jarvelin, M. R. ; Sørensen, T. I.A. ; Pennell, C. ; Felix, J. F. ; Jacobsson, B. ; Geller, F. ; Evans, D. M. ; Lawlor, D. A. / Maternal and fetal genetic contribution to gestational weight gain. In: International Journal of Obesity. 2018 ; Vol. 42, No. 4. pp. 775-784.
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abstract = "Background:Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methods:A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Results:Approximately 20{\%} of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10 {\^a} '8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.Conclusions:We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.",
author = "Warrington, {N. M.} and R. Richmond and B. Fenstra and R. Myhre and R. Gaillard and L. Paternoster and Wang, {C. A.} and Beaumont, {R. N.} and S. Das and M. Murcia and Barton, {S. J.} and A. Espinosa and E. Thiering and M. Atalay and N. Pitk{\"a}nen and I. Ntalla and Jonsson, {A. E.} and R. Freathy and V. Karhunen and Tiesler, {C. M.T.} and C. Allard and A. Crawford and Ring, {S. M.} and M. Melbye and P. Magnus and F. Rivadeneira and L. Skotte and T. Hansen and J. Marsh and M. Guxens and Holloway, {J. W.} and H. Grallert and Jaddoe, {V. W.V.} and Lowe, {W. L.} and T. Roumeliotaki and Hattersley, {A. T.} and V. Lindi and K. Pahkala and K. Panoutsopoulou and M. Standl and C. Flexeder and L. Bouchard and {Aagaard Nohr}, E. and {Santa Marina}, L. and M. Kogevinas and H. Niinikoski and G. Dedoussis and J. Heinrich and Reynolds, {R. M.} and T. Lakka and E. Zeggini and Raitakari, {O. T.} and L. Chatzi and Inskip, {H. M.} and M. Bustamante and Hivert, {M. F.} and Jarvelin, {M. R.} and S{\o}rensen, {T. I.A.} and C. Pennell and Felix, {J. F.} and B. Jacobsson and F. Geller and Evans, {D. M.} and Lawlor, {D. A.}",
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Warrington, NM, Richmond, R, Fenstra, B, Myhre, R, Gaillard, R, Paternoster, L, Wang, CA, Beaumont, RN, Das, S, Murcia, M, Barton, SJ, Espinosa, A, Thiering, E, Atalay, M, Pitkänen, N, Ntalla, I, Jonsson, AE, Freathy, R, Karhunen, V, Tiesler, CMT, Allard, C, Crawford, A, Ring, SM, Melbye, M, Magnus, P, Rivadeneira, F, Skotte, L, Hansen, T, Marsh, J, Guxens, M, Holloway, JW, Grallert, H, Jaddoe, VWV, Lowe, WL, Roumeliotaki, T, Hattersley, AT, Lindi, V, Pahkala, K, Panoutsopoulou, K, Standl, M, Flexeder, C, Bouchard, L, Aagaard Nohr, E, Santa Marina, L, Kogevinas, M, Niinikoski, H, Dedoussis, G, Heinrich, J, Reynolds, RM, Lakka, T, Zeggini, E, Raitakari, OT, Chatzi, L, Inskip, HM, Bustamante, M, Hivert, MF, Jarvelin, MR, Sørensen, TIA, Pennell, C, Felix, JF, Jacobsson, B, Geller, F, Evans, DM & Lawlor, DA 2018, 'Maternal and fetal genetic contribution to gestational weight gain', International Journal of Obesity, vol. 42, no. 4, pp. 775-784. https://doi.org/10.1038/ijo.2017.248

Maternal and fetal genetic contribution to gestational weight gain. / Warrington, N. M.; Richmond, R.; Fenstra, B.; Myhre, R.; Gaillard, R.; Paternoster, L.; Wang, C. A.; Beaumont, R. N.; Das, S.; Murcia, M.; Barton, S. J.; Espinosa, A.; Thiering, E.; Atalay, M.; Pitkänen, N.; Ntalla, I.; Jonsson, A. E.; Freathy, R.; Karhunen, V.; Tiesler, C. M.T.; Allard, C.; Crawford, A.; Ring, S. M.; Melbye, M.; Magnus, P.; Rivadeneira, F.; Skotte, L.; Hansen, T.; Marsh, J.; Guxens, M.; Holloway, J. W.; Grallert, H.; Jaddoe, V. W.V.; Lowe, W. L.; Roumeliotaki, T.; Hattersley, A. T.; Lindi, V.; Pahkala, K.; Panoutsopoulou, K.; Standl, M.; Flexeder, C.; Bouchard, L.; Aagaard Nohr, E.; Santa Marina, L.; Kogevinas, M.; Niinikoski, H.; Dedoussis, G.; Heinrich, J.; Reynolds, R. M.; Lakka, T.; Zeggini, E.; Raitakari, O. T.; Chatzi, L.; Inskip, H. M.; Bustamante, M.; Hivert, M. F.; Jarvelin, M. R.; Sørensen, T. I.A.; Pennell, C.; Felix, J. F.; Jacobsson, B.; Geller, F.; Evans, D. M.; Lawlor, D. A.

In: International Journal of Obesity, Vol. 42, No. 4, 01.04.2018, p. 775-784.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Maternal and fetal genetic contribution to gestational weight gain

AU - Warrington, N. M.

AU - Richmond, R.

AU - Fenstra, B.

AU - Myhre, R.

AU - Gaillard, R.

AU - Paternoster, L.

AU - Wang, C. A.

AU - Beaumont, R. N.

AU - Das, S.

AU - Murcia, M.

AU - Barton, S. J.

AU - Espinosa, A.

AU - Thiering, E.

AU - Atalay, M.

AU - Pitkänen, N.

AU - Ntalla, I.

AU - Jonsson, A. E.

AU - Freathy, R.

AU - Karhunen, V.

AU - Tiesler, C. M.T.

AU - Allard, C.

AU - Crawford, A.

AU - Ring, S. M.

AU - Melbye, M.

AU - Magnus, P.

AU - Rivadeneira, F.

AU - Skotte, L.

AU - Hansen, T.

AU - Marsh, J.

AU - Guxens, M.

AU - Holloway, J. W.

AU - Grallert, H.

AU - Jaddoe, V. W.V.

AU - Lowe, W. L.

AU - Roumeliotaki, T.

AU - Hattersley, A. T.

AU - Lindi, V.

AU - Pahkala, K.

AU - Panoutsopoulou, K.

AU - Standl, M.

AU - Flexeder, C.

AU - Bouchard, L.

AU - Aagaard Nohr, E.

AU - Santa Marina, L.

AU - Kogevinas, M.

AU - Niinikoski, H.

AU - Dedoussis, G.

AU - Heinrich, J.

AU - Reynolds, R. M.

AU - Lakka, T.

AU - Zeggini, E.

AU - Raitakari, O. T.

AU - Chatzi, L.

AU - Inskip, H. M.

AU - Bustamante, M.

AU - Hivert, M. F.

AU - Jarvelin, M. R.

AU - Sørensen, T. I.A.

AU - Pennell, C.

AU - Felix, J. F.

AU - Jacobsson, B.

AU - Geller, F.

AU - Evans, D. M.

AU - Lawlor, D. A.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background:Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methods:A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Results:Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10 â '8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.Conclusions:We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

AB - Background:Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methods:A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Results:Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10 â '8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.Conclusions:We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

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U2 - 10.1038/ijo.2017.248

DO - 10.1038/ijo.2017.248

M3 - Article

C2 - 28990592

AN - SCOPUS:85047253737

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JO - International Journal of Obesity

JF - International Journal of Obesity

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Warrington NM, Richmond R, Fenstra B, Myhre R, Gaillard R, Paternoster L et al. Maternal and fetal genetic contribution to gestational weight gain. International Journal of Obesity. 2018 Apr 1;42(4):775-784. https://doi.org/10.1038/ijo.2017.248