Genome-wide association study of offspring birth weight in 86?577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
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ABSTRACT:
SUBMITTER: Beaumont RN
PROVIDER: S-EPMC5886200 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
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Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
Beaumont Robin N RN Warrington Nicole M NM Cavadino Alana A Tyrrell Jessica J Nodzenski Michael M Horikoshi Momoko M Geller Frank F Myhre Ronny R Richmond Rebecca C RC Paternoster Lavinia L Bradfield Jonathan P JP Kreiner-Møller Eskil E Huikari Ville V Metrustry Sarah S Lunetta Kathryn L KL Painter Jodie N JN Hottenga Jouke-Jan JJ Allard Catherine C Barton Sheila J SJ Espinosa Ana A Marsh Julie A JA Potter Catherine C Zhang Ge G Ang Wei W Berry Diane J DJ Bouchard Luigi L Das Shikta S Hakonarson Hakon H Heikkinen Jani J Helgeland Øyvind Ø Hocher Berthold B Hofman Albert A Inskip Hazel M HM Jones Samuel E SE Kogevinas Manolis M Lind Penelope A PA Marullo Letizia L Medland Sarah E SE Murray Anna A Murray Jeffrey C JC Njølstad Pål R PR Nohr Ellen A EA Reichetzeder Christoph C Ring Susan M SM Ruth Katherine S KS Santa-Marina Loreto L Scholtens Denise M DM Sebert Sylvain S Sengpiel Verena V Tuke Marcus A MA Vaudel Marc M Weedon Michael N MN Willemsen Gonneke G Wood Andrew R AR Yaghootkar Hanieh H Muglia Louis J LJ Bartels Meike M Relton Caroline L CL Pennell Craig E CE Chatzi Leda L Estivill Xavier X Holloway John W JW Boomsma Dorret I DI Montgomery Grant W GW Murabito Joanne M JM Spector Tim D TD Power Christine C Järvelin Marjo-Ritta MR Bisgaard Hans H Grant Struan F A SFA Sørensen Thorkild I A TIA Jaddoe Vincent W VW Jacobsson Bo B Melbye Mads M McCarthy Mark I MI Hattersley Andrew T AT Hayes M Geoffrey MG Frayling Timothy M TM Hivert Marie-France MF Felix Janine F JF Hyppönen Elina E Lowe William L WL Evans David M DM Lawlor Debbie A DA Feenstra Bjarke B Freathy Rachel M RM
Human molecular genetics 20180201 4
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equat ...[more]
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Project description:ImportanceMaternal obesity, pregestational type 1 diabetes, and gestational diabetes have been reported to increase the risks for large birth weight and preterm birth in offspring. However, the associations for insulin-treated diabetes and non-insulin-treated type 2 diabetes, as well as the associations for joint diabetes disorders and maternal body mass index, with these outcomes are less well documented.ObjectiveTo examine associations of maternal diabetes disorders, separately and together with maternal underweight or obesity, with the offspring being large for gestational age and/or preterm at birth.Design, setting, and participantsThis population-based cohort study used nationwide registries to examine all live births (n = 649 043) between January 1, 2004, and December 31, 2014, in Finland. The study and data analysis were conducted from April 1, 2018, to October 10, 2018.ExposuresMaternal prepregnancy body mass index, pregestational diabetes with insulin treatment, pregestational type 2 diabetes without insulin treatment, and gestational diabetes.Main outcomes and measuresOffspring large for gestational age (LGA) at birth and preterm delivery. Logistic regression models were adjusted for offspring birth year; parity; and maternal age, country of birth, and smoking status.ResultsOf the 649 043 births, 4000 (0.62%) were delivered by mothers who had insulin-treated diabetes, 3740 (0.57%) by mothers who had type 2 diabetes, and 98 568 (15.2%) by mothers who had gestational diabetes. The mean (SD) age of mothers was 30.15 (5.37) years, and 588 100 mothers (90.6%) were born in Finland. Statistically significant interactions existed between maternal body mass index and diabetes on offspring LGA and prematurity (insulin-treated diabetes: LGA F = 3489.0 and prematurity F = 1316.4 [P < .001]; type 2 diabetes: LGA F = 147.3 and prematurity F = 21.9 [P < .001]; gestational diabetes: LGA F = 1374.6 and prematurity F = 434.3 [P < .001]). Maternal moderate obesity, compared with normal-weight mothers with no diabetes, was associated with a mildly increased risk of having an offspring LGA (1069 [3.5%] vs 5151 [1.5%]; adjusted odds ratio [aOR], 2.45; 95% CI, 2.29-2.62), and mothers with insulin-treated diabetes had markedly elevated risks of having an offspring LGA (1585 [39.6%] vs 5151 [1.5%]; aOR, 43.80; 95% CI, 40.88-46.93) and a preterm birth (1483 [37.1%] vs 17 481 [5.0%]; aOR, 11.17; 95% CI, 10.46-11.93). Mothers who were moderately obese with type 2 diabetes were at increased risks of LGA (132 [16.4%] vs 5151 [1.5%]; aOR, 12.44; 95% CI, 10.29-15.03) and prematurity (83 [10.3%] vs 17 481 [5.0%]; aOR, 2.14; 95% CI, 1.70-2.69). Mothers who were moderately obese with gestational diabetes had a milder risk of LGA (1195 [6.7%] vs 5151 [1.5%]; aOR, 4.72; 95% CI, 4.42-5.04). Among spontaneous deliveries, the risks were strongest for moderately preterm births, but insulin-treated diabetes was associated with an increased risk also for very and extremely preterm births.Conclusions and relevanceMaternal insulin-treated diabetes appeared to be associated with markedly increased risks for LGA and preterm births, whereas obesity in mothers with type 2 diabetes had mild to moderately increased risks; these findings may have implications for counseling and managing pregnancies.
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