Polar Overdominance Inheritance of DLK1 Variants Is Associated with Birth Weight in a Sex-Specific Manner

DLK1 is a paternally expressed gene encoding a transmembrane protein belonging to the Delta-Notch signaling family, increasingly recognized for its role in fetal growth regulation. This study explores the relationship between DLK1 genetic variants (SNV) and birth weight and the potential sex-specific differences in this association. This cross-sectional study consists of a sample of 949 participants (499 males and 450 females) with available birth weight information obtained from official birth certificates. Five DLK1 SNVs located within or near the DLK1 gene (rs1802710, rs876374, rs7155375, rs57098752, and rs7149242) were genotyped using Real-Time PCR with predesigned TaqMan™ Assays. Three SNVs (rs1802710, rs876374 and rs7149242) were significantly associated with birth weight in males, but not in females. Interestingly, heterozygous males had a higher mean birth weight than homozygous males. Further confirming this association, heterozygotes for these SNVs were more frequent among males with birth weight above the population mean (3.4 kg) compared to those below it. DLK1 variants are associated with birth weight in a sex-dependent manner and with an inheritance pattern compatible with polar overdominance. This places DLK1 as a genetic factor to be considered when evaluating health conditions related to higher or lower than normal birth weight.