Growth patterns of ABC participants according to SGA status
SGA children had significantly lower BMI z-score than AGA children at all three assessments conducted at 3.5, 7 and 11 years of age (Table and Figure ). BMI z-score showed no significant interaction between SGA status and age at assessment (p
0.254) (Table and Figure ).
Differences in birth weight and BMI z-score
BMI z-score Growth by SGA status
A total of 37 candidate SNPs for obesity were successfully genotyped (Table ), and their relationship with BMI z-score was tested. There was no indication of a deviation from Hardy Weinberg equilibrium (HWE), except for one SNP (rs7903146) which was excluded from further analysis. Using a prespecified FDR threshold at α
], we determined that 27 SNPs were significantly associated with the BMI z-score in at least one of the four analyses: stratified by AGA and SGA children, after adjustment for SGA status, and interaction with SGA status (Table ).
Variants associated with BMI z-score in AGA children
A total of 16 variants: rs2286385 (ADIPOR2), rs6013029 and rs6020712 (CTNNBL1), rs7138803 (FAIM2), rs8050136 and rs9939609 (FTO), rs1042725 (HMGA2), rs12970134, rs17700633, rs17782313, rs4450508, and rs502933 (MC4R), rs2293855 (MTMR9), rs10508503 (PTER), rs10913469 (SEC16B), and rs7498665 (SH2B1) in 10 genes were found to be significantly associated with BMI z-score in AGA children after correction for multiple testing (Table ). The impact on BMI z-score increase varied with the tested variant allele from 0.100 (rs7498665 SH2B1) to 0.309 (rs6020712 CTNNBL1).
Variants associated with BMI z-score in SGA children
Ten variants in seven genes were significantly associated with BMI z-score in SGA children after correction for multiple testing (Table ). The impact on BMI z-score increase varied from 0.133 (rs2815752 NEGR1) to 0.458 (rs6020395 CTNNBL1). In contrast to those born AGA, none of the 5 variants in MC4R were associated with increasing BMI z-score in those born SGA.
Variants associated with BMI z-score after adjustment for SGA status
A total of 20 variants: rs2286385 (ADIPOR2), rs6265 (BDNF), rs16986921, rs6013029, rs6020395, rs6020712, rs6020846, rs6096781, and rs6125962 (CTNNBL1), rs6499640, rs8050136, and rs9939609 (FTO), rs1042725 (HMGA2), rs11084753 (KCTD15), rs12970134, rs17782313, rs4450508, and rs502933 (MC4R), rs10508503 (PTER), and rs10913469 (SEC16B) showed significant association after adjustment SGA status and also correction for multiple testing. BMI z-score increased with all tested obesity risk variant alleles ranging from 0.087 (rs1042725 HMGA2) to 0.303 (rs6013029 CTNNBL1).
Variants associated with interaction between BMI z-score and SGA status
A total of eight variants: rs1424233 (MAF), rs12970134 and rs17782313, (MC4R), rs2293855 (MTMR9), rs2568958 and rs2815752 (NEGR1), rs10508503 (PTER), and rs7498665 (SH2B1) showed significant interaction with SGA status. Two of these variant (MC4R and PTER) also showed a significant association with BMI z-score among the whole cohort with adjustment for SGA status, however, their effect was only observed among those born AGA, with no effect in SGA. Of the remaining obesity risk variants showing a significant interaction with SGA status, two variants in NEGR1 were associated with increased BMI in those born SGA but no effect in those born AGA, while SH2B1 obesity risk variant showed increased BMI in those born SGA and reduced BMI in those born AGA. There was a significant interaction between the MAF variant and SGA status, and reduced BMI in the SGA group (Table ). However, there were no significant effects on BMI when the association was tested within those born SGA and AGA.