The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study

Margrit Urbanek*, M. Geoffrey Hayes, Loren L. Armstrong, Jean Morrison, Lynn P. Lowe, Sylvia E. Badon, Doug Scheftner, Anna Pluzhnikov, David Levine, Cathy C. Laurie, Caitlin McHugh, Christine M. Ackerman, Daniel B. Mirel, Kimberly F. Doheny, Cong Guo, Denise M. Scholtens, Alan R. Dyer, Boyd E. Metzger, Timothy E. Reddy, Nancy J. CoxWilliam L. Lowe

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Newborns characterized as large and small for gestational age are at risk for increased mortality and morbidity during the first year of life as well as for obesity and dysglycemia as children and adults. The intrauterine environment and fetal genes contribute to the fetal size at birth. To define the genetic architecture underlying the newborn size, we performed a genome-wide association study (GWAS) in 4281 newborns in four ethnic groups from the Hyperglycemia and Adverse Pregnancy Outcome Study. We tested for association with newborn anthropometric traits (birth length, headcircumference, birth weight, percent fatmassandsumof skinfolds)andnewborn metabolic traits (cord glucose and C-peptide) under three models. Model 1 adjusted for field center, ancestry, neonatal gender, gestational age at delivery, parity, maternal age at oral glucose tolerance test (OGTT); Model 2 adjusted for Model 1 covariates, maternal body mass index (BMI) at OGTT, maternal height at OGTT, maternal mean arterial pressure at OGTT, maternal smoking and drinking; Model 3 adjusted for Model 2 covariates, maternal glucose and C-peptide atOGTT. Strong evidence for associationwasobserved with measures of newborn adiposity (sum of skinfolds model 3 Z-score 7.356, P = 1.90 × 10-13, and to a lesser degree fat mass and birth weight) and a region on Chr3q25.31 mapping between CCNL and LEKR1. These findings were replicated in an independent cohort of 2296 newborns. This region has previously been shown to be associated with birth weight in Europeans. The current study suggests that association of this locus with birth weight is secondary to an effect on fat as opposed to lean body mass.

Original languageEnglish (US)
Article numberddt168
Pages (from-to)3583-3596
Number of pages14
JournalHuman molecular genetics
Volume22
Issue number17
DOIs
StatePublished - Sep 1 2013

Fingerprint

Genome-Wide Association Study
Adiposity
Chromosomes
Newborn Infant
Glucose Tolerance Test
Birth Weight
Mothers
C-Peptide
Gestational Age
Fats
Parturition
Glucose
Maternal Age
Pregnancy Outcome
Parity
Ethnic Groups
Hyperglycemia
Drinking
Arterial Pressure
Body Mass Index

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Urbanek, Margrit ; Hayes, M. Geoffrey ; Armstrong, Loren L. ; Morrison, Jean ; Lowe, Lynn P. ; Badon, Sylvia E. ; Scheftner, Doug ; Pluzhnikov, Anna ; Levine, David ; Laurie, Cathy C. ; McHugh, Caitlin ; Ackerman, Christine M. ; Mirel, Daniel B. ; Doheny, Kimberly F. ; Guo, Cong ; Scholtens, Denise M. ; Dyer, Alan R. ; Metzger, Boyd E. ; Reddy, Timothy E. ; Cox, Nancy J. ; Lowe, William L. / The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study. In: Human molecular genetics. 2013 ; Vol. 22, No. 17. pp. 3583-3596.
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abstract = "Newborns characterized as large and small for gestational age are at risk for increased mortality and morbidity during the first year of life as well as for obesity and dysglycemia as children and adults. The intrauterine environment and fetal genes contribute to the fetal size at birth. To define the genetic architecture underlying the newborn size, we performed a genome-wide association study (GWAS) in 4281 newborns in four ethnic groups from the Hyperglycemia and Adverse Pregnancy Outcome Study. We tested for association with newborn anthropometric traits (birth length, headcircumference, birth weight, percent fatmassandsumof skinfolds)andnewborn metabolic traits (cord glucose and C-peptide) under three models. Model 1 adjusted for field center, ancestry, neonatal gender, gestational age at delivery, parity, maternal age at oral glucose tolerance test (OGTT); Model 2 adjusted for Model 1 covariates, maternal body mass index (BMI) at OGTT, maternal height at OGTT, maternal mean arterial pressure at OGTT, maternal smoking and drinking; Model 3 adjusted for Model 2 covariates, maternal glucose and C-peptide atOGTT. Strong evidence for associationwasobserved with measures of newborn adiposity (sum of skinfolds model 3 Z-score 7.356, P = 1.90 × 10-13, and to a lesser degree fat mass and birth weight) and a region on Chr3q25.31 mapping between CCNL and LEKR1. These findings were replicated in an independent cohort of 2296 newborns. This region has previously been shown to be associated with birth weight in Europeans. The current study suggests that association of this locus with birth weight is secondary to an effect on fat as opposed to lean body mass.",
author = "Margrit Urbanek and Hayes, {M. Geoffrey} and Armstrong, {Loren L.} and Jean Morrison and Lowe, {Lynn P.} and Badon, {Sylvia E.} and Doug Scheftner and Anna Pluzhnikov and David Levine and Laurie, {Cathy C.} and Caitlin McHugh and Ackerman, {Christine M.} and Mirel, {Daniel B.} and Doheny, {Kimberly F.} and Cong Guo and Scholtens, {Denise M.} and Dyer, {Alan R.} and Metzger, {Boyd E.} and Reddy, {Timothy E.} and Cox, {Nancy J.} and Lowe, {William L.}",
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Urbanek, M, Hayes, MG, Armstrong, LL, Morrison, J, Lowe, LP, Badon, SE, Scheftner, D, Pluzhnikov, A, Levine, D, Laurie, CC, McHugh, C, Ackerman, CM, Mirel, DB, Doheny, KF, Guo, C, Scholtens, DM, Dyer, AR, Metzger, BE, Reddy, TE, Cox, NJ & Lowe, WL 2013, 'The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study', Human molecular genetics, vol. 22, no. 17, ddt168, pp. 3583-3596. https://doi.org/10.1093/hmg/ddt168

The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study. / Urbanek, Margrit; Hayes, M. Geoffrey; Armstrong, Loren L.; Morrison, Jean; Lowe, Lynn P.; Badon, Sylvia E.; Scheftner, Doug; Pluzhnikov, Anna; Levine, David; Laurie, Cathy C.; McHugh, Caitlin; Ackerman, Christine M.; Mirel, Daniel B.; Doheny, Kimberly F.; Guo, Cong; Scholtens, Denise M.; Dyer, Alan R.; Metzger, Boyd E.; Reddy, Timothy E.; Cox, Nancy J.; Lowe, William L.

In: Human molecular genetics, Vol. 22, No. 17, ddt168, 01.09.2013, p. 3583-3596.

Research output: Contribution to journalArticle

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T1 - The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study

AU - Urbanek, Margrit

AU - Hayes, M. Geoffrey

AU - Armstrong, Loren L.

AU - Morrison, Jean

AU - Lowe, Lynn P.

AU - Badon, Sylvia E.

AU - Scheftner, Doug

AU - Pluzhnikov, Anna

AU - Levine, David

AU - Laurie, Cathy C.

AU - McHugh, Caitlin

AU - Ackerman, Christine M.

AU - Mirel, Daniel B.

AU - Doheny, Kimberly F.

AU - Guo, Cong

AU - Scholtens, Denise M.

AU - Dyer, Alan R.

AU - Metzger, Boyd E.

AU - Reddy, Timothy E.

AU - Cox, Nancy J.

AU - Lowe, William L.

PY - 2013/9/1

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N2 - Newborns characterized as large and small for gestational age are at risk for increased mortality and morbidity during the first year of life as well as for obesity and dysglycemia as children and adults. The intrauterine environment and fetal genes contribute to the fetal size at birth. To define the genetic architecture underlying the newborn size, we performed a genome-wide association study (GWAS) in 4281 newborns in four ethnic groups from the Hyperglycemia and Adverse Pregnancy Outcome Study. We tested for association with newborn anthropometric traits (birth length, headcircumference, birth weight, percent fatmassandsumof skinfolds)andnewborn metabolic traits (cord glucose and C-peptide) under three models. Model 1 adjusted for field center, ancestry, neonatal gender, gestational age at delivery, parity, maternal age at oral glucose tolerance test (OGTT); Model 2 adjusted for Model 1 covariates, maternal body mass index (BMI) at OGTT, maternal height at OGTT, maternal mean arterial pressure at OGTT, maternal smoking and drinking; Model 3 adjusted for Model 2 covariates, maternal glucose and C-peptide atOGTT. Strong evidence for associationwasobserved with measures of newborn adiposity (sum of skinfolds model 3 Z-score 7.356, P = 1.90 × 10-13, and to a lesser degree fat mass and birth weight) and a region on Chr3q25.31 mapping between CCNL and LEKR1. These findings were replicated in an independent cohort of 2296 newborns. This region has previously been shown to be associated with birth weight in Europeans. The current study suggests that association of this locus with birth weight is secondary to an effect on fat as opposed to lean body mass.

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