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Type: Journal article
Title: Variants near CCNL1/LEKR1 and in ADCY5 and fetal growth characteristics in different trimesters
Author: Mook-Kanamori, D.
Marsh, J.
Warrington, N.
Taal, H.
Newnham, J.
Beilin, L.
Lye, S.
Palmer, L.
Hofman, A.
Steegers, E.
Pennell, C.
Early Growth Genetics
Jaddoe, V.
Citation: Journal of Clinical Endocrinology and Metabolism, 2011; 96(5):810-815
Publisher: Endocrine Society
Issue Date: 2011
ISSN: 0021-972X
Statement of
Dennis O. Mook-Kanamori, Julie A. Marsh, Nicole M. Warrington, H. Rob Taal, John P. Newnham, Lawrie J. Beilin, Stephen J. Lye, Lyle J. Palmer, Albert Hofman, Eric A. P. Steegers, Craig E. Pennell, the Early Growth Genetics Consortium, and Vincent W. V. Jaddoe
Abstract: Common variants near CCNL1/LEKR1 and in ADCY5 are associated with symmetric and asymmetric fetal growth restriction, respectively. CONTEXT: A recent genome-wide association study identified variants near CCNL1/LEKR1 (rs900400) and in ADCY5 (rs9883204) to be associated with birth weight. We examined the associations of these variants with fetal growth characteristics in different trimesters, with a main interest in the timing of the associations and the affected body proportions. METHODS: We used data from two prospective cohort studies from fetal life onward in The Netherlands and Australia. Repeated fetal ultrasound examinations were performed to measure head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW). Analyses were based on a total group of 3909 subjects. RESULTS: The C-allele of rs900400 was associated in second trimester with smaller fetal HC and FL, and in third trimester with smaller HC, AC, FL, and EFW. For each C-allele, the combined effect estimate for EFW in third trimester was −18.6 g (95% confidence interval, −27.5, −9.7 g; P = 4.2 × 10−5). The C-allele of rs9883204 was not associated with fetal growth characteristics in second trimester but was associated with restriction of all growth characteristics, except HC, in third trimester and at birth. For each C-allele, the combined effect estimate was −16.9 g (95% confidence interval, −26.8, −7.0 g; P = 8.4 × 10−4) for EFW in third trimester. Both genetic variants were associated with lower birth and placenta weight. CONCLUSIONS: Our results suggest that a genetic variant of rs900400 leads to symmetric growth restriction from early pregnancy onward, whereas a genetic variant of rs9883204 leads to asymmetric growth restriction, characterized by a relatively larger HC, from third trimester.
Keywords: Early Growth Genetics Consortium; Chromosomes, Human, Pair 3; Humans; Adenylate Cyclase; Cyclins; Data Interpretation, Statistical; Linear Models; Cohort Studies; Longitudinal Studies; Prospective Studies; Cross-Sectional Studies; Fetal Development; Pregnancy; Pregnancy Trimesters; Gene Frequency; Genotype; Alleles; Adult; Western Australia; Netherlands; Female; Genetic Variation
Rights: Copyright © 2011 by The Endocrine Society
RMID: 0020136625
DOI: 10.1210/jc.2010-2316
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Appears in Collections:Translational Health Science publications

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