Genetic origins of low birth weight.

PURPOSE OF REVIEW

Smaller size at birth is associated with a higher risk of type 2 diabetes in later life, but the mechanisms behind this association are poorly understood. Genetic variants which influence susceptibility to type 2 diabetes via effects on insulin secretion or action are good candidates for association with birth weight because foetal insulin is a key foetal growth factor. This review will focus on recent progress in identifying associations between common genetic variants and birth weight.

RECENT FINDINGS

Foetal genetic variants at two loci (near CCNL1 and in ADCY5) were robustly associated with birth weight via the foetal genotype in the first genome-wide association study of birth weight. The birth weight-lowering allele at ADCY5 also predisposes to type 2 diabetes. In addition, evidence from studies of other type 2 diabetes loci is accumulating for association between the foetal risk alleles at CDKAL1 and HHEX-IDE and lower birth weight, and the maternal risk alleles at GCK and TCF7L2 and higher birth weight.

SUMMARY

The associations with birth weight at ADCY5, CDKAL1 and HHEX-IDE support the foetal insulin hypothesis, which proposed that type 2 diabetes and lower birth weight could be two phenotypes of the same genotype. The associations at GCK and TCF7L2 illustrate that maternal genes are also important determinants of birth weight.