A Genome-Wide Association Study of Early Spontaneous Preterm Delivery

Heping Zhang*, Don A. Baldwin, Radek K. Bukowski, Samuel Parry, Yaji Xu, Chi Song, William W. Andrews, George R. Saade, M. Sean Esplin, Yoel Sadovsky, Uma M. Reddy, John Ilekis, Michael Varner, Joseph R. Biggio, Stephanie Wilson Archer, Rachel L. Copper, Pamela B. Files, Stacy L. Harris, Ian Blair, Rita Leite & 31 others Margaret L. Zimmerle, Janet L. Brandon, Sonia Jordan, Angela Jones, Kelly Vorwaller, Sharon Quinn, Valerie S. Morby, Kathleen N. Jolley, Julie A. Postma, Kei Hoi Cheung, Basso Donna Del, Xiaobo Guo, Buqu Hu, Hao Huang, Lina Jin, Analisa L. Lin, Charles C. Lu, Laura Ment, Lauren Perley, Laura Jeanne Simone, Feifei Xiao, Dwight J. Rouse, Donna Allard, Ronald Wapner, Michelle Divito, Sabine Bousleiman, Vilmarie Carmona, Rosely Alcon, Katty Saravia, Alan M. Peaceman, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR)

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Preterm birth is the leading cause of infant morbidity and mortality. Despite extensive research, the genetic contributions to spontaneous preterm birth (SPTB) are not well understood. Term controls were matched with cases by race/ethnicity, maternal age, and parity prior to recruitment. Genotyping was performed using Affymetrix SNP Array 6.0 assays. Statistical analyses utilized PLINK to compare allele occurrence rates between case and control groups, and incorporated quality control and multiple-testing adjustments. We analyzed DNA samples from mother-infant pairs from early SPTB cases (20 0/7 -33 6/7 weeks, 959 women and 979 neonates) and term delivery controls (39 0/7 -41 6/7 weeks, 960 women and 985 neonates). For validation purposes, we included an independent validation cohort consisting of early SPTB cases (293 mothers and 243 infants) and term controls (200 mothers and 149 infants). Clustering analysis revealed no population stratification. Multiple maternal SNPs were identified with association P-values between 10 × 10 -5 and 10 × 10 -6 . The most significant maternal SNP was rs17053026 on chromosome 3 with an odds ratio (OR) 0.44 with a P-value of 1.0 × 10 -6 . Two neonatal SNPs reached the genome-wide significance threshold, including rs17527054 on chromosome 6p22 with a P-value of 2.7 × 10 -12 and rs3777722 on chromosome 6q27 with a P-value of 1.4 × 10 -10 . However, we could not replicate these findings after adjusting for multiple comparisons in a validation cohort. This is the first report of a genome-wide case-control study to identify single nucleotide polymorphisms (SNPs) that correlate with SPTB.

Original languageEnglish (US)
Pages (from-to)217-226
Number of pages10
JournalGenetic Epidemiology
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

Genome-Wide Association Study
Premature Birth
Single Nucleotide Polymorphism
Mothers
Chromosomes
Newborn Infant
Genome
Social Adjustment
Chromosomes, Human, Pair 3
Maternal Age
Infant Mortality
Parity
Quality Control
Cluster Analysis
Case-Control Studies
Alleles
Odds Ratio
Morbidity
Control Groups
DNA

Keywords

  • Association analysis
  • Obstetric
  • Premature birth

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

Cite this

Zhang, H., Baldwin, D. A., Bukowski, R. K., Parry, S., Xu, Y., Song, C., ... Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR) (2015). A Genome-Wide Association Study of Early Spontaneous Preterm Delivery. Genetic Epidemiology, 39(3), 217-226. https://doi.org/10.1002/gepi.21887
Zhang, Heping ; Baldwin, Don A. ; Bukowski, Radek K. ; Parry, Samuel ; Xu, Yaji ; Song, Chi ; Andrews, William W. ; Saade, George R. ; Esplin, M. Sean ; Sadovsky, Yoel ; Reddy, Uma M. ; Ilekis, John ; Varner, Michael ; Biggio, Joseph R. ; Archer, Stephanie Wilson ; Copper, Rachel L. ; Files, Pamela B. ; Harris, Stacy L. ; Blair, Ian ; Leite, Rita ; Zimmerle, Margaret L. ; Brandon, Janet L. ; Jordan, Sonia ; Jones, Angela ; Vorwaller, Kelly ; Quinn, Sharon ; Morby, Valerie S. ; Jolley, Kathleen N. ; Postma, Julie A. ; Cheung, Kei Hoi ; Del, Basso Donna ; Guo, Xiaobo ; Hu, Buqu ; Huang, Hao ; Jin, Lina ; Lin, Analisa L. ; Lu, Charles C. ; Ment, Laura ; Perley, Lauren ; Simone, Laura Jeanne ; Xiao, Feifei ; Rouse, Dwight J. ; Allard, Donna ; Wapner, Ronald ; Divito, Michelle ; Bousleiman, Sabine ; Carmona, Vilmarie ; Alcon, Rosely ; Saravia, Katty ; Peaceman, Alan M. ; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR). / A Genome-Wide Association Study of Early Spontaneous Preterm Delivery. In: Genetic Epidemiology. 2015 ; Vol. 39, No. 3. pp. 217-226.
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Zhang, H, Baldwin, DA, Bukowski, RK, Parry, S, Xu, Y, Song, C, Andrews, WW, Saade, GR, Esplin, MS, Sadovsky, Y, Reddy, UM, Ilekis, J, Varner, M, Biggio, JR, Archer, SW, Copper, RL, Files, PB, Harris, SL, Blair, I, Leite, R, Zimmerle, ML, Brandon, JL, Jordan, S, Jones, A, Vorwaller, K, Quinn, S, Morby, VS, Jolley, KN, Postma, JA, Cheung, KH, Del, BD, Guo, X, Hu, B, Huang, H, Jin, L, Lin, AL, Lu, CC, Ment, L, Perley, L, Simone, LJ, Xiao, F, Rouse, DJ, Allard, D, Wapner, R, Divito, M, Bousleiman, S, Carmona, V, Alcon, R, Saravia, K, Peaceman, AM & Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR) 2015, 'A Genome-Wide Association Study of Early Spontaneous Preterm Delivery', Genetic Epidemiology, vol. 39, no. 3, pp. 217-226. https://doi.org/10.1002/gepi.21887

A Genome-Wide Association Study of Early Spontaneous Preterm Delivery. / Zhang, Heping; Baldwin, Don A.; Bukowski, Radek K.; Parry, Samuel; Xu, Yaji; Song, Chi; Andrews, William W.; Saade, George R.; Esplin, M. Sean; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John; Varner, Michael; Biggio, Joseph R.; Archer, Stephanie Wilson; Copper, Rachel L.; Files, Pamela B.; Harris, Stacy L.; Blair, Ian; Leite, Rita; Zimmerle, Margaret L.; Brandon, Janet L.; Jordan, Sonia; Jones, Angela; Vorwaller, Kelly; Quinn, Sharon; Morby, Valerie S.; Jolley, Kathleen N.; Postma, Julie A.; Cheung, Kei Hoi; Del, Basso Donna; Guo, Xiaobo; Hu, Buqu; Huang, Hao; Jin, Lina; Lin, Analisa L.; Lu, Charles C.; Ment, Laura; Perley, Lauren; Simone, Laura Jeanne; Xiao, Feifei; Rouse, Dwight J.; Allard, Donna; Wapner, Ronald; Divito, Michelle; Bousleiman, Sabine; Carmona, Vilmarie; Alcon, Rosely; Saravia, Katty; Peaceman, Alan M.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR).

In: Genetic Epidemiology, Vol. 39, No. 3, 01.03.2015, p. 217-226.

Research output: Contribution to journalArticle

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T1 - A Genome-Wide Association Study of Early Spontaneous Preterm Delivery

AU - Zhang, Heping

AU - Baldwin, Don A.

AU - Bukowski, Radek K.

AU - Parry, Samuel

AU - Xu, Yaji

AU - Song, Chi

AU - Andrews, William W.

AU - Saade, George R.

AU - Esplin, M. Sean

AU - Sadovsky, Yoel

AU - Reddy, Uma M.

AU - Ilekis, John

AU - Varner, Michael

AU - Biggio, Joseph R.

AU - Archer, Stephanie Wilson

AU - Copper, Rachel L.

AU - Files, Pamela B.

AU - Harris, Stacy L.

AU - Blair, Ian

AU - Leite, Rita

AU - Zimmerle, Margaret L.

AU - Brandon, Janet L.

AU - Jordan, Sonia

AU - Jones, Angela

AU - Vorwaller, Kelly

AU - Quinn, Sharon

AU - Morby, Valerie S.

AU - Jolley, Kathleen N.

AU - Postma, Julie A.

AU - Cheung, Kei Hoi

AU - Del, Basso Donna

AU - Guo, Xiaobo

AU - Hu, Buqu

AU - Huang, Hao

AU - Jin, Lina

AU - Lin, Analisa L.

AU - Lu, Charles C.

AU - Ment, Laura

AU - Perley, Lauren

AU - Simone, Laura Jeanne

AU - Xiao, Feifei

AU - Rouse, Dwight J.

AU - Allard, Donna

AU - Wapner, Ronald

AU - Divito, Michelle

AU - Bousleiman, Sabine

AU - Carmona, Vilmarie

AU - Alcon, Rosely

AU - Saravia, Katty

AU - Peaceman, Alan M.

AU - Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR)

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Preterm birth is the leading cause of infant morbidity and mortality. Despite extensive research, the genetic contributions to spontaneous preterm birth (SPTB) are not well understood. Term controls were matched with cases by race/ethnicity, maternal age, and parity prior to recruitment. Genotyping was performed using Affymetrix SNP Array 6.0 assays. Statistical analyses utilized PLINK to compare allele occurrence rates between case and control groups, and incorporated quality control and multiple-testing adjustments. We analyzed DNA samples from mother-infant pairs from early SPTB cases (20 0/7 -33 6/7 weeks, 959 women and 979 neonates) and term delivery controls (39 0/7 -41 6/7 weeks, 960 women and 985 neonates). For validation purposes, we included an independent validation cohort consisting of early SPTB cases (293 mothers and 243 infants) and term controls (200 mothers and 149 infants). Clustering analysis revealed no population stratification. Multiple maternal SNPs were identified with association P-values between 10 × 10 -5 and 10 × 10 -6 . The most significant maternal SNP was rs17053026 on chromosome 3 with an odds ratio (OR) 0.44 with a P-value of 1.0 × 10 -6 . Two neonatal SNPs reached the genome-wide significance threshold, including rs17527054 on chromosome 6p22 with a P-value of 2.7 × 10 -12 and rs3777722 on chromosome 6q27 with a P-value of 1.4 × 10 -10 . However, we could not replicate these findings after adjusting for multiple comparisons in a validation cohort. This is the first report of a genome-wide case-control study to identify single nucleotide polymorphisms (SNPs) that correlate with SPTB.

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KW - Obstetric

KW - Premature birth

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Zhang H, Baldwin DA, Bukowski RK, Parry S, Xu Y, Song C et al. A Genome-Wide Association Study of Early Spontaneous Preterm Delivery. Genetic Epidemiology. 2015 Mar 1;39(3):217-226. https://doi.org/10.1002/gepi.21887