We wish to investigate the associations between birth outcomes, (primarily gestational age and birth weight) and SNPs with proven roles in biochemical phenotypes. Key pathways include the inflammatory response and vascular function, which has important implications for utero-placental function. We have recently performed a genome wide assocaition study of mulitple biochemistry phenotypes in the InCHIANTI study (Melzer et al PloS Genetics, May 08), that has identified, or taken to GWAS significance, many variants altering biochemical traits. This study and other recent genome-wide and large-scale association studies have provided robust evidence (P values less than 5 x 10-8) that common genetic variants, marked by key SNPs, influence the levels of various inflammatory cytokines, clotting factors, and susceptibility to aneurysm. This makes them excellent candidates for altering fetal growth and or gestational age and greatly increases the prior odds that they will influence genetic susceptibility to preterm birth through these pathways. In addition, SNPs have been identified which alter the circulating serum levels of various nutrients, hormones and growth factors, including Vitamin A, each of which is also a potential candidate for influencing susceptibility to preterm birth. In the case of Vitamin A , a known teratogen, the SNP that alters Vitamin A may alter risk of miscarriages or fetal abnormalities.

In this study we propose to test the hypothesis that each selected "functional" SNP is associated with fetal growth and or gestational age.

We wish to genotype the selected SNPs in all ALSPAC mothers and children in order to assess associations between fetal growth gestational age and both maternal and fetal genotypes.

ALSPAC is the largest and best UK study for investigating the genetics of fetal growth and perinatal outcomes as it is well-powered to detect small genetic effects, it has the availability of both maternal and fetal DNA and has detailed clinical data on birth size and pregnancy outcomes as well as other relevant maternal phenotypes. RAINE in collaboration with Lyle Palmer, and NFBC with Mark McCarthy, Leena Peltonen and Marjo-Riita Jarvelin are other potential sources of replication/meta-analysis for fetal effects.