Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals.
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.


METHODS
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 (n(max) = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623); and 3) all published data (n(max) = 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.
Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom.
Tuomas O
TO
Kilpeläinen
Marcel
M
den Hoed
Ken K
KK
Ong
Anders
A
Grøntved
Soren
S
Brage
Karen
K
Jameson
Cyrus
C
Cooper
Kay-Tee
KT
Khaw
Ulf
U
Ekelund
Nicholas J
NJ
Wareham
Ruth J F
RJ
Loos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001724:Birth Weight / Q000235:genetics*; D015992:Body Mass Index; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D055815:Young Adult
C502207:MTCH2 protein, human; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
BJOG. 2008 Jun;115(7):886-93
18485168
Am J Obstet Gynecol. 1998 May;178(5):1022-6
9609578
Science. 2007 May 11;316(5826):889-94
17434869
Horm Res Paediatr. 2010;73(4):275-80
20215774
Hum Mol Genet. 2010 Feb 1;19(3):545-52
19880856
BMC Med Genet. 2009 Mar 05;10:21
19265514
Semin Perinatol. 2008 Oct;32(5):371-4
18929161
PLoS Med. 2010 May 25;7(5):e1000284
20520848
Nat Genet. 2010 May;42(5):430-5
20372150
Int J Obes Relat Metab Disord. 2003 Jul;27(7):755-77
12821960
Nat Genet. 2009 Jan;41(1):18-24
19079260
Behav Genet. 1997 Jul;27(4):325-51
9519560
Am J Clin Nutr. 2010 Sep;92(3):594-602
20592134
Diabetes. 2008 Jan;57(1):95-101
17942823
PLoS Genet. 2007 Jul;3(7):e115
17658951
Int J Obes (Lond). 2010 Sep;34(9):1365-70
20351740
Am J Hum Genet. 2009 Jul;85(1):106-11
19559399
Br J Cancer. 1999 Jul;80 Suppl 1:95-103
10466767
Nat Genet. 2008 Jun;40(6):768-75
18454148
Am J Clin Nutr. 2002 Apr;75(4):676-82
11916753
BMC Med Genet. 2010 Apr 09;11:58
20380707
Int J Obes Relat Metab Disord. 1995 Jun;19(6):397-402
7550524
Nat Genet. 2009 Jan;41(1):25-34
19079261
Nat Genet. 2009 Feb;41(2):157-9
19151714
Early Hum Dev. 2005 Oct;81(10):823-31
16085375
Twin Res. 1998 Sep;1(3):123-30
10051336
Genet Med. 2007 Aug;9(8):528-35
17700391
Nature. 2009 Apr 16;458(7240):894-8
19234441
BMJ. 2001 Dec 8;323(7325):1331-5
11739217
Int J Epidemiol. 2005 Dec;34(6):1234-42
15964908
Nat Cell Biol. 2010 Jun;12(6):553-562
20436477
Int J Obes (Lond). 2005 Oct;29(10):1222-9
15795752
PLoS Genet. 2009 Aug;5(8):e1000599
19680540
J Mol Med (Berl). 2009 May;87(5):537-46
19255736
J Clin Endocrinol Metab. 2008 Apr;93(4):1501-5
18252780
Am J Epidemiol. 2007 Apr 1;165(7):734-41
17311798
Diabet Med. 2005 Jul;22(7):921-30
15975109