Smallness for gestational age interacts with high mobility group A2 gene genetic variation to modulate height

Area of Science:

• Human genetics
• Growth and development
• Population studies

Background:

• Height variability is significantly influenced by genetic factors.
• Identifying specific genetic variants affecting height has been challenging.
• Smallness for gestational age (SGA) is a known risk factor for adult short stature.

Purpose of the Study:

• To investigate the contribution of the HMGA2 rs1042725 single nucleotide polymorphism (SNP) to height variability in a French population.
• To determine the impact of rs1042725 on SGA status and adult height in SGA individuals.

Main Methods:

• Genotyping of the rs1042725 SNP in 4710 healthy participants (DESIR cohort) and 1303 individuals (normal birth weight and SGA) from the Haguenau study.
• Statistical analysis to assess the association of rs1042725 with height variability and SGA status.

Main Results:

• The rs1042725 SNP was associated with increased height in the general cohort (0.36 cm per C allele, P=0.004).
• A stronger effect on height was observed in SGA individuals (0.94 cm per C allele, P=0.009), especially in men (1.45 cm per C allele, P=0.005).
• In SGA males, the rs1042725 variant was linked to more frequent height catch-up.

Conclusions:

• The HMGA2 rs1042725 SNP contributes to height variability in European populations.
• This variant shows an enhanced effect on height in individuals born small for gestational age, promoting catch-up growth.