Haplotype-based heritability estimations reveal gestational duration as a maternal trait and fetal size measurements at birth as fetal traits in human pregnancy

Unlike other commonly studied complex traits, pregnancy phenotypes like gestational duration and fetal size measurements at birth are conjointly determined by maternal and fetal genomes. Current approaches of heritability estimation based upon an individual9s genotype information are limited in addressing confounding by shared alleles between mother and fetus. Here, we propose a novel approach of treating the mother-child pairs as a single analytical unit with three haplotypes - maternal transmitted (m1), maternal non-transmitted (m2) and paternal transmitted (p1). Using our haplotype-based approach, we estimate the SNP heritability (h ĥ^2) of gestational duration and gestational duration adjusted fetal size measurements at birth in 10,375 mother-child pairs. The results reveal that variance in gestational duration is mainly attributable to m1 and m2 (h ĥ_m1^2=14% and h ĥ_m2^2=10%). In contrast, variance in fetal size measurements at birth are mainly attributable to m1 and p1. Variance in birth weight is attributable to both m1 and p1 (h ĥ_m1^2=19.9% and h ĥ_p1^2=13.3%). However, variance in birth length (h ĥ_m1^2=24.5% and h ĥ_p1^2=4.0%) and head circumference (h ĥ_m1^2=33.1% and h ĥ_p1^2=12.3%) are largely attributable to m1. Our results suggest that gestational duration is primarily determined by the maternal genome whereas fetal size measurements at birth are primarily determined by fetal genome. In addition, the difference between (h ĥ_m1^2-h ĥ_m2^2) and h ĥ_p1^2 suggests a greater contribution of the maternal transmitted haplotype than the paternal transmitted haplotype to birth length and head circumference. Our haplotype-based GCTA approach (H-GCTA) resolves explicit contributions of maternal and fetal genomes to SNP heritability of pregnancy phenotypes.