Genetic association study of preterm birth and gestational age in a population-based case-control study in Peru.
J Neonatal Perinatal Med
; 17(5): 689-704, 2024.
Article
em En
| MEDLINE
| ID: mdl-39302385
ABSTRACT
BACKGROUND:
Preterm birth (PTB) affects â¼15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women.METHODS:
PTB cases delivered≥20 weeks' butâ<â37 weeks' gestation, while controls delivered at term (≥37 weeks but <42 weeks). Multivariable regressions were used to identify genetic markers for PTB and GA (â¼6 million SNPs), adjusting for maternal age and the first two genetic principal components. In silico functional analysis was conducted among top signals detected with an arbitrary Pâ<â1.0×10-5 . We sought to replicate genetic markers for PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers.RESULTS:
Mean GA was 30 ± 4 weeks in PTB cases (Nâ=â933) and 39 ± 1 in the controls (Nâ=â1,279). No associatiosn were identified at genome-wide level. Nominal PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Nominal GA variants were enriched in intronic regions and cancer pathways. Variants in WNT4 associated with GA in Europeans were replicated in our study. A genetic risk score was associated with a 2-day longer GA (Pâ=â0.002) in our sample.CONCLUSIONS:
This study identified various signals suggestively associated with PTB and GA in pregnant Peruvian women. None of these variants overlapped with signals previously identified in Europeans.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Idade Gestacional
/
Polimorfismo de Nucleotídeo Único
/
Nascimento Prematuro
/
Estudo de Associação Genômica Ampla
Limite:
Adult
/
Female
/
Humans
/
Newborn
/
Pregnancy
País/Região como assunto:
America do sul
/
Peru
Idioma:
En
Revista:
J Neonatal Perinatal Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Holanda