Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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26978208
TITLE
Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.
ABSTRACT
IMPORTANCE NlmCategory: OBJECTIVE
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 NlmCategory: OBJECTIVE
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. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.
DESIGN, SETTING, AND PARTICIPANTS NlmCategory: METHODS
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. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. 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 NlmCategory: METHODS
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. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. 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. 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 NlmCategory: METHODS
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. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. 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. 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. Offspring birth weight from 18 studies.
RESULTS NlmCategory: RESULTS
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. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. 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. 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. Offspring birth weight from 18 studies. 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 -2 g) 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 NlmCategory: CONCLUSIONS
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. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. 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. 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. Offspring birth weight from 18 studies. 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 -2 g) 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. 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.
DATE PUBLISHED
2016 Mar 15
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2016/03/16 06:00
pubmed 2016/03/16 06:00
medline 2016/03/24 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Tyrrell J Tyrrell Jessica J Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, United Kingdom2European Centre for Environment and Human Health, University of Exeter, the Knowledge Spa, Truro, United Kingdom.
Richmond RC Richmond Rebecca C RC School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, United Kingdom4The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands5Medical Research Council Inte.
Palmer TM Palmer Tom M TM Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom7Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom.
Feenstra B Feenstra Bjarke B Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Rangarajan J Rangarajan Janani J Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Metrustry S Metrustry Sarah S Department of Twin Research, King's College London, St Thomas' Hospital, London, United Kingdom.
Cavadino A Cavadino Alana A Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts, and the London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom12Population, Policy and Practice, UCL Institute of Child He.
Paternoster L Paternoster Lavinia L Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom.
Armstrong LL Armstrong Loren L LL Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
De Silva NM De Silva N Maneka G NM Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom.
Wood AR Wood Andrew R AR Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, United Kingdom.
Horikoshi M Horikoshi Momoko M Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, United Kingdom15Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Geller F Geller Frank F Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Myhre R Myhre Ronny R Division of Epidemiology, Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway.
Bradfield JP Bradfield Jonathan P JP Center for Applied Genomics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Kreiner-Møller E Kreiner-Møller Eskil E Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, and Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
Huikari V Huikari Ville V Institute of Health Sciences, University of Oulu, Oulu, Finland.
Painter JN Painter Jodie N JN QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Australia.
Hottenga JJ Hottenga Jouke-Jan JJ EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands22Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
Allard C Allard Catherine C Department of Mathematics, Universite de Sherbrooke, Quebec City, Quebec, Canada24Centre de recherché du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec City, Quebec, Canada.
Berry DJ Berry Diane J DJ Population, Policy and Practice, UCL Institute of Child Health, University College London, United Kingdom.
Bouchard L Bouchard Luigi L Centre de recherché du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec City, Quebec, Canada25ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Saguenay, Quebec City, Quebec, Canada26Department of Biochemistry, Université de Sherbrooke.
Das S Das Shikta S Department of Primary Care and Public Health, Imperial College London, United Kingdom.
Evans DM Evans David M DM School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, United Kingdom5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom28University of Queensland Diamantin.
Hakonarson H Hakonarson Hakon H Center for Applied Genomics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania29Division of Human Genetics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania30Department of Pediatrics, Perelman School of Medicine, Unive.
Hayes MG Hayes M Geoffrey MG Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Heikkinen J Heikkinen Jani J FIMM Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland.
Hofman A Hofman Albert A Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands54Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Knight B Knight Bridget B Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, United Kingdom.
Lind PA Lind Penelope A PA QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Australia.
McCarthy MI McCarthy Mark I MI Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, United Kingdom15Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom33Oxford National Institute for Health Research (NIHR) Biomedical Researc.
McMahon G McMahon George G School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, United Kingdom.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Australia.
Melbye M Melbye Mads M Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark34Department of Medicine, Stanford University School of Medicine, Stanford, California.
Morris AP Morris Andrew P AP Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom35Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
Nodzenski M Nodzenski Michael M Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Reichetzeder C Reichetzeder Christoph C Institute of Nutritional Science, University of Potsdam, Germany37Center for Cardiovascular Research/Charité, Berlin, Germany.
Ring SM Ring Susan M SM School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, United Kingdom5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom.
Sebert S Sebert Sylvain S Institute of Health Sciences, University of Oulu, Oulu, Finland38Department of Epidemiology and Biostatistics, School of Public Health, Medical Research Council-Health Protection Agency Centre for Environment and Health, Faculty of Medicine, Imperial Coll.
Sengpiel V Sengpiel Verena V Department of Obstetrics and Gynecology, Sahlgrenska Academy, Sahgrenska University Hospital, Gothenburg, Sweden.
Sørensen TI Sørensen Thorkild I A TI Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom40Institute of Preventive Medicine, Bispebjerg and Frederiksberg University Hospital, Capital Region, Copenhagen, Denmark41Novo Nordisk Foundation Center fo.
Willemsen G Willemsen Gonneke G EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands22Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
de Geus EJ de Geus Eco J C EJ EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands22Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Australia.
Spector TD Spector Tim D TD Department of Twin Research, King's College London, St Thomas' Hospital, London, United Kingdom.
Power C Power Christine C Population, Policy and Practice, UCL Institute of Child Health, University College London, United Kingdom.
Järvelin MR Järvelin Marjo-Riitta MR Institute of Health Sciences, University of Oulu, Oulu, Finland38Department of Epidemiology and Biostatistics, School of Public Health, Medical Research Council-Health Protection Agency Centre for Environment and Health, Faculty of Medicine, Imperial Coll.
Bisgaard H Bisgaard Hans H Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, and Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
Grant SF Grant Struan F A SF Center for Applied Genomics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania29Division of Human Genetics, the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania30Department of Pediatrics, Perelman School of Medicine, Unive.
Nohr EA Nohr Ellen A EA Research Unit of Obstetrics & Gynecology, Institute of Clinical Research, University of Southern Denmark, Odense.
Jaddoe VW Jaddoe Vincent W VW The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands32Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands46Department of Pediatrics, Erasmus MC, University Medic.
Jacobsson B Jacobsson Bo B Division of Epidemiology, Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway39Department of Obstetrics and Gynecology, Sahlgrenska Academy, Sahgrenska University Hospital, Gothenburg, Sweden.
Murray JC Murray Jeffrey C JC Department of Pediatrics, University of Iowa, Iowa City.
Hocher B Hocher Berthold B Institute of Nutritional Science, University of Potsdam, Germany48The First Affiliated Hospital of Jinan University, Guangzhou, China.
Hattersley AT Hattersley Andrew T AT Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, United Kingdom.
Scholtens DM Scholtens Denise M DM Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Davey Smith G Davey Smith George G School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, United Kingdom5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom.
Hivert MF Hivert Marie-France MF Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, Massachusetts50Diabetes Center, Massachusetts General Hospital, Boston51Department of Medicine, Universite de Sherbrooke, Quebec City, Quebec, Canada.
Felix JF Felix Janine F JF The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands32Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands46Department of Pediatrics, Erasmus MC, University Medic.
Hyppönen E Hyppönen Elina E Population, Policy and Practice, UCL Institute of Child Health, University College London, United Kingdom52Centre for Population Health Research, School of Health Sciences, and Sansom Institute, University of South Australia, Adelaide53South Australian He.
Lowe WL Jr Lowe William L WL Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Frayling TM Frayling Timothy M TM Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, United Kingdom.
Lawlor DA Lawlor Debbie A DA School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, United Kingdom5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom.
Freathy RM Freathy Rachel M RM Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, United Kingdom5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom.
Early Growth Genetics (EGG) Consortium
INVESTIGATORS
JOURNAL
VOLUME: 315
ISSUE: 11
TITLE: JAMA
ISOABBREVIATION: JAMA
YEAR: 2016
MONTH: Mar
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1538-3598
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: JAMA
COUNTRY: United States
ISSNLINKING: 0098-7484
NLMUNIQUEID: 7501160
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
ErratumIn JAMA. 2016 Apr 19;315(15):1661 27092840
GRANTS
GRANTID AGENCY COUNTRY
G1001799 Medical Research Council United Kingdom
G0701603 Medical Research Council United Kingdom
G0500070 Medical Research Council United Kingdom
104150/Z/14/Z Wellcome Trust United Kingdom
MC_UU_12013/3 Medical Research Council United Kingdom
MC_QA137853 Medical Research Council United Kingdom
MC_UU_1201/1 Medical Research Council United Kingdom
MR/N01104X/1 Medical Research Council United Kingdom
MC_PC_15018 Medical Research Council United Kingdom
R01 DK10324 NIDDK NIH HHS United States
MC_UU_12013/1 Medical Research Council United Kingdom
MC_UU_12013/4 Medical Research Council United Kingdom
WT088806 Wellcome Trust United Kingdom
G0601261 Medical Research Council United Kingdom
MC_UU_12013/5 Medical Research Council United Kingdom
G9815508 Medical Research Council United Kingdom
MC_UU_1201/4 Medical Research Council United Kingdom
MR/J012165/1 Medical Research Council United Kingdom
WT094529MA Wellcome Trust United Kingdom
102215 Wellcome Trust United Kingdom
104150 Wellcome Trust United Kingdom
CIHR Canada
R01 HD056465 NICHD NIH HHS United States
P30 ES013508 NIEHS NIH HHS United States
R01 DK103246 NIDDK NIH HHS United States
098395 Wellcome Trust United Kingdom
MC_UU_1201/1/5 Medical Research Council United Kingdom
WT083431MF Wellcome Trust United Kingdom
WT098017 Wellcome Trust United Kingdom
323195 European Research Council International
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Birth Weight genetics
Blood Glucose genetics
Blood Pressure genetics
Body Mass Index genetics
Diabetes Mellitus, Type 2 genetics
European Continental Ancestry Group genetics
Fasting blood
Female blood
Genotype blood
Humans blood
Infant, Newborn blood
Mendelian Randomization Analysis blood
Obesity genetics
Polymorphism, Single Nucleotide genetics
Pregnancy genetics
Triglycerides genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Blood Glucose
0 Triglycerides
OTHER ID's
OTHERID SOURCE
EMS67630 NLM