Scientists from deCODE genetics have mapped 243 sequence variants affecting fetal growth, separating maternal genome and fetal genome. It sheds light on the relationships between hypertension, diabetes and fetal growth.

Valgerdur Steinthorsdottir, Kari Stefansson and Thorhildur Juliusdottir authors on the paper.

In a paper published in Nature genetics today, Scientists from deCODE genetics, a fully owned subsidiary of Amgen, report sequence variants that associate with birth weight and demonstrate how these variants affect birth weight through both the maternal and fetal genomes. Although birth weight is associated with a range of health outcomes, it is debated how much these relationships are through the fetal genome or affected by the intrauterine environment, and hence the maternal genome.

A total of 243 fetal growth variants are reported and 141 of them were grouped into four main clusters based on separating the effect of the variant on birth weight though the maternal versus fetal genome. The majority of variants show an effect only in the fetus and a quarter of those show evidence of a parent-of-origin specific effect on birth weight i.e. the effect on the fetus differs depending on whether the child inherited the variant from the mother or the father. Some variants have an effect only in the mother but around 30% affect birth weight both through the maternal and fetal genomes, where for some the effect is in the same direction, no matter whether from mother or father, while for others the effect is in opposite directions.

Polygenic risk score analysis of disease-associated variants revealed that variants associating with blood pressure do not associate with birth weight when in the maternal genome but in the fetal genome the blood pressure raising allele correlates with lower birth weight. Variants that associate with the risk of type 2 diabetes associate with birth weight through both the maternal and fetal genomes but in opposite directions. In the mother, the risk alleles correlate with higher birth weight but when in the fetus they correlate with lower birth weight.

“The ability to analyze directly the effect of each of the transmitted alleles and the maternal non-transmitted allele allows us to separate what happens through the mother from a direct effect on birth weight through the fetal genome,” says Valgerdur Steinthorsdottir scientist at deCODE Genetics and author on the paper

The study reports an expanded GWAS meta-analysis of 400,000 children, 270,000 mothers and 60,000 fathers, combining data from the Icelandic Birth Register for 125,000 newborns and their parents with public summary level fetal growth data on children and mothers from the Early Growth Genetics Consortium and UK Biobank. The effects of the fetal, maternal and paternal genomes on birth weight were analyzed and the study further includes analysis of birth length and ponderal index.

“It is clear from these results that in our beginnings we are not only shaped by the half of our maternal genome that is transmitted to us but also the untransmitted half,” says Kari Stefansson CEO of deCODE genetics. “Here we show how the influence of the two halves can be separated.”