No evidence for association between BMI and 10 candidate genes at ages 4, 7 and 10 in a large UK sample of twins.
BACKGROUND
Over the last decade, associations between Body Mass Index (BMI) and a variety of candidate genes have been reported, but samples have almost all been limited to adults. The purpose of the present study was to test the developmental origins of some of these associations in a large longitudinal sample of children.


METHODS
For 10 single-nucleotide polymorphisms (SNPs) in candidate genes reported to be associated with BMI in adults, we examined associations with BMI in a sample of 5000 children (2500 twin pairs) with BMI data at 4, 7 and 10 years. Association analyses were performed using the Quantitative Transmission Disequilibrium Test and we corrected for multiple testing using the False Discovery Rate.


RESULTS
Despite having 80% power to detect associations that account for as little as 0.2% of the variance of BMI, none of the 10 SNPs were significantly associated with BMI at any age, although two SNPs showed trends in the expected direction.


CONCLUSIONS
The lack of association for these ten previously reported associations, despite our large sample size, is typical of associations between candidate genes and complex traits. However, some of the reported SNP associations with BMI might emerge as we continue to follow the sample into adolescence and adulthood. This report highlights the importance of developmentally appropriate candidate genes.
Haworth
Claire M A
CM
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK. Claire.Haworth@iop.kcl.ac.uk
Butcher
Lee M
LM
Docherty
Sophia J
SJ
Wardle
Jane
J
Plomin
Robert
R
D000367:Age Factors; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D004200:Diseases in Twins / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012737:Sex Factors; D006113:United Kingdom / Q000453:epidemiology
D005819:Genetic Markers