TY - JOUR
T1 - Obesity-susceptibility loci have a limited influence on birth weight
T2 - a meta-analysis of up to 28,219 individuals
AU - Oskari Kilpeläinen, Tuomas
AU - den Hoed, Marcel
AU - Ong, Ken K
AU - Grøntved, Anders
AU - Brage, Soren
AU - Jameson, Karen
AU - Cooper, Cyrus
AU - Khaw, Kay-Tee
AU - Ekelund, Ulf
AU - Wareham, Nicholas J
AU - Loos, Ruth J F
AU - Early Growth Genetics Consortium
PY - 2011/4/1
Y1 - 2011/4/1
N2 - Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (nmax = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (nmax = 10,623); and 3) all published data (nmax = 14,837). Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.
AB - Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (nmax = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (nmax = 10,623); and 3) all published data (nmax = 14,837). Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Alleles
KW - Birth Weight
KW - Body Mass Index
KW - Female
KW - Genetic Loci
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Membrane Transport Proteins
KW - Middle Aged
KW - Mitochondrial Membrane Transport Proteins
KW - Mitochondrial Proteins
KW - Obesity
KW - Proteins
KW - Young Adult
U2 - 10.3945/ajcn.110.000828
DO - 10.3945/ajcn.110.000828
M3 - Journal article
C2 - 21248185
SN - 0002-9165
VL - 93
SP - 851
EP - 860
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 4
ER -
