Genetic determinants of adiponectin regulation revealed by pregnancy

Marie France Hivert; Denise M. Scholtens; Catherine Allard; Michael Nodzenski; Luigi Bouchard; Diane Brisson; Lynn P. Lowe; Ian McDowell; Tim Reddy; Zari Dastani; J. Brent Richards; M. Geoffrey Hayes; William L. Lowe

doi:10.1002/oby.21805

Genetic determinants of adiponectin regulation revealed by pregnancy

Marie France Hivert^*, Denise M. Scholtens, Catherine Allard, Michael Nodzenski, Luigi Bouchard, Diane Brisson, Lynn P. Lowe, Ian McDowell, Tim Reddy, Zari Dastani, J. Brent Richards, M. Geoffrey Hayes, William L. Lowe

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Objective: This study investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation. Methods: A genome-wide association study was conducted in 1,322 pregnant women from the Hyperglycemia and Adverse Pregnancy Outcome Study with adiponectin measured at ∼28 weeks of gestation. Variants reaching P < 5×10⁻⁵ for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N = 522; ECOGENE-21 N = 174) were selected. Results: In the combined meta-analysis, the maternal T allele of rs900400 located on chr3q25 (near LEKR1/CCNL1) was associated with lower maternal adiponectin (β ± standard error [SE] = −0.18 ± 0.03 standard deviation [SD] of adiponectin per risk allele; P = 1.5 × 10⁻⁸; N = 2,004; multivariable adjusted models). In contrast, rs900400 showed only nominal association with adiponectin in a large sample of nonpregnant women (β ± SE = −0.012 ± 0.006; P = 0.05; N = 16,678 women from the ADIPOgen consortium). The offspring rs900400 T risk allele was associated with greater neonatal skinfold thickness (β ±SE = 0.19 ± 0.04 SD per risk allele; P = 4.1×10⁻⁸; N = 1,489) and higher cord blood leptin (β ± SE = 0.28 ± 0.05 log-leptin per risk allele; P = 8.2 × 10⁻⁹; N = 502), but not with cord blood adiponectin (P = 0.23; N = 495). The T allele of rs900400 was associated with higher expression of TIPARP in adipocytes. Conclusions: These investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.

Original language	English (US)
Pages (from-to)	935-944
Number of pages	10
Journal	Obesity
Volume	25
Issue number	5
DOIs	https://doi.org/10.1002/oby.21805
State	Published - May 2017

Funding

The authors are indebted to the participants of the HAPO Study at the following centers: Newcastle and Brisbane, Australia; Bridgetown, Barbados; Toronto, Ontario, Canada; Hong Kong; Bangkok, Thailand; Belfast and Manchester, UK; Bellflower, California; Chicago, Illinois; Cleveland, Ohio; and Providence, Rhode Island. Gen3G investigators would like to acknowledge the participants, the research staff from the endocrinology group at the Centre de Recherche clinique of the Centre Hospitalier de l'Universit\u00E9 de Sherbrooke (CR-CHUS), the clinical and research staff of the Clinique de Pr\u00E9l\u00E8vement en Grossesse du CHUS, and the clinical staff from the CHUS Obstetric Department. ECOGENE-21 Birth Cohort investigators are thankful to the participants, the research staff from the ECOGENE-21 Clinical Research Center, and the clinical staff from the CHA universitaire r\u00E9gional de Chicoutimi Obstetric Department. HAPO genome-wide arrays data are available through dbGaP: http://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id=phs000096.v4.p1.

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/oby.21805

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@article{23d77525d1c847edbd0ea8a85c395af2,

title = "Genetic determinants of adiponectin regulation revealed by pregnancy",

abstract = "Objective: This study investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation. Methods: A genome-wide association study was conducted in 1,322 pregnant women from the Hyperglycemia and Adverse Pregnancy Outcome Study with adiponectin measured at ∼28 weeks of gestation. Variants reaching P < 5×10−5 for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N = 522; ECOGENE-21 N = 174) were selected. Results: In the combined meta-analysis, the maternal T allele of rs900400 located on chr3q25 (near LEKR1/CCNL1) was associated with lower maternal adiponectin (β ± standard error [SE] = −0.18 ± 0.03 standard deviation [SD] of adiponectin per risk allele; P = 1.5 × 10−8; N = 2,004; multivariable adjusted models). In contrast, rs900400 showed only nominal association with adiponectin in a large sample of nonpregnant women (β ± SE = −0.012 ± 0.006; P = 0.05; N = 16,678 women from the ADIPOgen consortium). The offspring rs900400 T risk allele was associated with greater neonatal skinfold thickness (β ±SE = 0.19 ± 0.04 SD per risk allele; P = 4.1×10−8; N = 1,489) and higher cord blood leptin (β ± SE = 0.28 ± 0.05 log-leptin per risk allele; P = 8.2 × 10−9; N = 502), but not with cord blood adiponectin (P = 0.23; N = 495). The T allele of rs900400 was associated with higher expression of TIPARP in adipocytes. Conclusions: These investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.",

author = "Hivert, {Marie France} and Scholtens, {Denise M.} and Catherine Allard and Michael Nodzenski and Luigi Bouchard and Diane Brisson and Lowe, {Lynn P.} and Ian McDowell and Tim Reddy and Zari Dastani and Richards, {J. Brent} and Hayes, {M. Geoffrey} and Lowe, {William L.}",

note = "Publisher Copyright: {\textcopyright} 2017 The Obesity Society",

year = "2017",

month = may,

doi = "10.1002/oby.21805",

language = "English (US)",

volume = "25",

pages = "935--944",

journal = "Obesity",

issn = "1930-7381",

publisher = "John Wiley and Sons Inc.",

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TY - JOUR

T1 - Genetic determinants of adiponectin regulation revealed by pregnancy

AU - Hivert, Marie France

AU - Scholtens, Denise M.

AU - Allard, Catherine

AU - Nodzenski, Michael

AU - Bouchard, Luigi

AU - Brisson, Diane

AU - Lowe, Lynn P.

AU - McDowell, Ian

AU - Reddy, Tim

AU - Dastani, Zari

AU - Richards, J. Brent

AU - Hayes, M. Geoffrey

AU - Lowe, William L.

PY - 2017/5

Y1 - 2017/5

N2 - Objective: This study investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation. Methods: A genome-wide association study was conducted in 1,322 pregnant women from the Hyperglycemia and Adverse Pregnancy Outcome Study with adiponectin measured at ∼28 weeks of gestation. Variants reaching P < 5×10−5 for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N = 522; ECOGENE-21 N = 174) were selected. Results: In the combined meta-analysis, the maternal T allele of rs900400 located on chr3q25 (near LEKR1/CCNL1) was associated with lower maternal adiponectin (β ± standard error [SE] = −0.18 ± 0.03 standard deviation [SD] of adiponectin per risk allele; P = 1.5 × 10−8; N = 2,004; multivariable adjusted models). In contrast, rs900400 showed only nominal association with adiponectin in a large sample of nonpregnant women (β ± SE = −0.012 ± 0.006; P = 0.05; N = 16,678 women from the ADIPOgen consortium). The offspring rs900400 T risk allele was associated with greater neonatal skinfold thickness (β ±SE = 0.19 ± 0.04 SD per risk allele; P = 4.1×10−8; N = 1,489) and higher cord blood leptin (β ± SE = 0.28 ± 0.05 log-leptin per risk allele; P = 8.2 × 10−9; N = 502), but not with cord blood adiponectin (P = 0.23; N = 495). The T allele of rs900400 was associated with higher expression of TIPARP in adipocytes. Conclusions: These investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.

AB - Objective: This study investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation. Methods: A genome-wide association study was conducted in 1,322 pregnant women from the Hyperglycemia and Adverse Pregnancy Outcome Study with adiponectin measured at ∼28 weeks of gestation. Variants reaching P < 5×10−5 for de novo genotyping in two replication cohorts (Genetics of Glycemic regulation in Gestation and Growth N = 522; ECOGENE-21 N = 174) were selected. Results: In the combined meta-analysis, the maternal T allele of rs900400 located on chr3q25 (near LEKR1/CCNL1) was associated with lower maternal adiponectin (β ± standard error [SE] = −0.18 ± 0.03 standard deviation [SD] of adiponectin per risk allele; P = 1.5 × 10−8; N = 2,004; multivariable adjusted models). In contrast, rs900400 showed only nominal association with adiponectin in a large sample of nonpregnant women (β ± SE = −0.012 ± 0.006; P = 0.05; N = 16,678 women from the ADIPOgen consortium). The offspring rs900400 T risk allele was associated with greater neonatal skinfold thickness (β ±SE = 0.19 ± 0.04 SD per risk allele; P = 4.1×10−8; N = 1,489) and higher cord blood leptin (β ± SE = 0.28 ± 0.05 log-leptin per risk allele; P = 8.2 × 10−9; N = 502), but not with cord blood adiponectin (P = 0.23; N = 495). The T allele of rs900400 was associated with higher expression of TIPARP in adipocytes. Conclusions: These investigations of adipokines during pregnancy and early life suggest that rs900400 has a role in adipocyte function.

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Genetic determinants of adiponectin regulation revealed by pregnancy

Abstract

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UN SDGs

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