Genetic Epidemiology, Psychiatric Genetics, Asthma 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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PMID
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
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
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
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
Offspring birth weight from 18 studies.
RESULTS NlmCategory: 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 -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
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 2016/03/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Tyrrell J
Richmond RC
Palmer TM
Feenstra B
Rangarajan J
Metrustry S
Cavadino A
Paternoster L
Armstrong LL
De Silva NM
Wood AR
Horikoshi M
Geller F
Myhre R
Bradfield JP
Kreiner-Moller E
Huikari V
Painter JN
Hottenga JJ
Allard C
Berry DJ
Bouchard L
Das S
Evans DM
Hakonarson H
Hayes MG
Heikkinen J
Hofman A
Knight B
Lind PA
McCarthy MI
McMahon G
Medland SE
Melbye M
Morris AP
Nodzenski M
Reichetzeder C
Ring SM
Sebert S
Sengpiel V
Sorensen TI
Willemsen G
de Geus EJ
Martin NG
Spector TD
Power C
Jarvelin MR
Bisgaard H
Grant SF
Nohr EA
Jaddoe VW
Jacobsson B
Murray JC
Hocher B
Hattersley AT
Scholtens DM
Davey Smith G
Hivert MF
Felix JF
Hypponen E
Lowe WL Jr
Frayling TM
Lawlor DA
Freathy RM
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
GRANTS
GRANTID AGENCY COUNTRY
104150/Z/14/Z Wellcome Trust United Kingdom
MC_UU_1201/1 Medical Research Council United Kingdom
MC_UU_1201/1/5 Medical Research Council United Kingdom
MC_UU_1201/4 Medical Research Council United Kingdom
R01 DK10324 NIDDK NIH HHS United States
WT083431MF Wellcome Trust United Kingdom
WT088806 Wellcome Trust United Kingdom
WT094529MA Wellcome Trust United Kingdom
WT098017 Wellcome Trust United Kingdom
Canadian Institutes of Health Research Canada
GENERAL NOTE
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