Maternal Age at Menarche Gene Polymorphisms Are Associated with Offspring Birth Weight

Abstract

In this study, the association between maternal age at menarche (AAM)-related polymorphisms and offspring birth weight (BW) was studied. The work was performed on a sample of 716 pregnant women and their newborns. All pregnant women underwent genotyping of 50 SNPs of AAM candidate genes. Regression methods (linear and Model-Based Multifactor Dimensionality Reduction (MB-MDR)) with permutation procedures (the indicator p_perm was calculated) were used to identify the correlation between SNPs and newborn weight (transformed BW values were analyzed) and in silico bioinformatic examination was applied to assess the intended functionality of BW-associated loci. Four AAM-related genetic variants were BW-associated including genes such as <i>POMC</i> (rs7589318) (β_additive = 0.202/p_perm = 0.015), <i>KDM3B</i> (rs757647) (β_recessive = 0.323/p_perm = 0.005), <i>INHBA</i> (rs1079866) (β_additive = 0.110/p_perm = 0.014) and <i>NKX2-1</i> (rs999460) (β<i>_recessive</i> = -0.176/p_perm = 0.015). Ten BW-significant models of interSNPs interactions (p_perm ≤ 0.001) were identified for 20 polymorphisms. SNPs rs7538038 <i>KISS1</i>, rs713586 <i>RBJ</i>, rs12324955 <i>FTO</i> and rs713586 <i>RBJ</i>-rs12324955 <i>FTO</i> two-locus interaction were included in the largest number of BW-associated models (30% models each). BW-associated AAM-linked 22 SNPs and 350 proxy loci were functionally related to 49 genes relevant to pathways such as the hormone biosynthesis/process and female/male gonad development. In conclusion, maternal AMM-related genes polymorphism is associated with the offspring BW.