Genetic risk score for prediction of newborn adiposity and large-for-gestational-age birth

Reeti Chawla, Sylvia E. Badon, Janani Rangarajan, Anna C. Reisetter, Loren L. Armstrong, Lynn P. Lowe, Margrit Urbanek, Boyd E. Metzger, M. Geoffrey Hayes, Denise M. Scholtens*, William L. Lowe

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Context: Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes.

Objective: This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth.

Setting and Design: Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association withnewbornsize. GRS's for birth weight andsum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses.

Participants: Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai).

Outcome Measures: Birth weight >90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes.

Results: After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, bodymass index, height, blood pressureandglucose, 25and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P le; 1.6 × 10-19) and improved prediction of birth weight and SSF >90th percentilewhenadded to a baseline model incorporating the covariates listed above.

Conclusions: A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors.

Original languageEnglish (US)
Pages (from-to)E2377-E2386
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number11
DOIs
StatePublished - Nov 1 2014

Fingerprint

Adiposity
Polymorphism
Gestational Age
Single Nucleotide Polymorphism
Nucleotides
Parturition
Newborn Infant
Birth Weight
Obesity
Mothers
Outcome Assessment (Health Care)
Pregnancy Outcome
Parity
Hyperglycemia
Meta-Analysis
Blood
Genes
Smoking
Genotype
Alcohols

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Chawla, Reeti ; Badon, Sylvia E. ; Rangarajan, Janani ; Reisetter, Anna C. ; Armstrong, Loren L. ; Lowe, Lynn P. ; Urbanek, Margrit ; Metzger, Boyd E. ; Hayes, M. Geoffrey ; Scholtens, Denise M. ; Lowe, William L. / Genetic risk score for prediction of newborn adiposity and large-for-gestational-age birth. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 11. pp. E2377-E2386.
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abstract = "Context: Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes.Objective: This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth.Setting and Design: Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association withnewbornsize. GRS's for birth weight andsum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses.Participants: Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai).Outcome Measures: Birth weight >90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes.Results: After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, bodymass index, height, blood pressureandglucose, 25and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P le; 1.6 × 10-19) and improved prediction of birth weight and SSF >90th percentilewhenadded to a baseline model incorporating the covariates listed above.Conclusions: A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors.",
author = "Reeti Chawla and Badon, {Sylvia E.} and Janani Rangarajan and Reisetter, {Anna C.} and Armstrong, {Loren L.} and Lowe, {Lynn P.} and Margrit Urbanek and Metzger, {Boyd E.} and Hayes, {M. Geoffrey} and Scholtens, {Denise M.} and Lowe, {William L.}",
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Genetic risk score for prediction of newborn adiposity and large-for-gestational-age birth. / Chawla, Reeti; Badon, Sylvia E.; Rangarajan, Janani; Reisetter, Anna C.; Armstrong, Loren L.; Lowe, Lynn P.; Urbanek, Margrit; Metzger, Boyd E.; Hayes, M. Geoffrey; Scholtens, Denise M.; Lowe, William L.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 11, 01.11.2014, p. E2377-E2386.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic risk score for prediction of newborn adiposity and large-for-gestational-age birth

AU - Chawla, Reeti

AU - Badon, Sylvia E.

AU - Rangarajan, Janani

AU - Reisetter, Anna C.

AU - Armstrong, Loren L.

AU - Lowe, Lynn P.

AU - Urbanek, Margrit

AU - Metzger, Boyd E.

AU - Hayes, M. Geoffrey

AU - Scholtens, Denise M.

AU - Lowe, William L.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Context: Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes.Objective: This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth.Setting and Design: Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association withnewbornsize. GRS's for birth weight andsum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses.Participants: Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai).Outcome Measures: Birth weight >90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes.Results: After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, bodymass index, height, blood pressureandglucose, 25and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P le; 1.6 × 10-19) and improved prediction of birth weight and SSF >90th percentilewhenadded to a baseline model incorporating the covariates listed above.Conclusions: A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors.

AB - Context: Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes.Objective: This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth.Setting and Design: Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association withnewbornsize. GRS's for birth weight andsum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses.Participants: Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai).Outcome Measures: Birth weight >90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes.Results: After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, bodymass index, height, blood pressureandglucose, 25and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P le; 1.6 × 10-19) and improved prediction of birth weight and SSF >90th percentilewhenadded to a baseline model incorporating the covariates listed above.Conclusions: A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors.

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DO - 10.1210/jc.2013-4221

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