The role of genetics in fetal programming of adult cardiometabolic disease

Carlos Sánchez-Soriano, Ewan R. Pearson, Rebecca M. Reynolds (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

Abstract

Disturbances affecting early development have broad repercussions on the individual's health during infancy and adulthood. Multiple observational studies throughout the years have shown that alterations of fetal growth are associated with increased cardiometabolic disease risks. However, the genetic component of this association only started to be investigated in the last 40 years, when single genes with distinct effects were investigated. Birth weight (BW), commonly reported as the outcome of developmental growth, has been estimated to be 20% to 60% heritable. Through Genome-Wide Association (GWA) meta-analyses, 190 different loci have been identified being associated with BW, and while many of these loci designate genes involved in glucose and lipid metabolism, with clear ties to fetal development, the role of others is not yet understood. In addition, due to its influence over the intrauterine environment, the maternal genotype also plays an important part in the determination of offspring BW, with the same loci having independent effects of different magnitude or even direction. There is still much to uncover regarding the genetic determinants of BW and the interactions between maternal, offspring, and even paternal genotype. To fully understand these, diverse and novel cohorts from multiple ancestries collecting extensive neonatal phenotype will be needed. This review compiles, chronologically, the main findings in the investigation of the genetics of BW.

Original languageEnglish
Number of pages8
JournalJournal of Developmental Origins of Health and Disease
Early online date28 Jun 2021
DOIs
Publication statusE-pub ahead of print - 28 Jun 2021

Keywords

  • birth weight
  • Fetal programming
  • genetics
  • Keywords:
  • metabolic disease

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