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https://hdl.handle.net/2440/88445
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Type: | Journal article |
Title: | FTO genotype is associated with phenotypic variability of body mass index |
Author: | Yang, J. Loos, R. Powell, J. Medland, S. Speliotes, E. Chasman, D. Rose, L. Thorleifsson, G. Steinthorsdottir, V. Mägi, R. Waite, L. Smith, A. Yerges-Armstrong, L. Monda, K. Hadley, D. Mahajan, A. Li, G. Kapur, K. Vitart, V. Huffman, J. et al. |
Citation: | Nature, 2012; 490(7419):267-273 |
Publisher: | Nature Publishing Group |
Issue Date: | 2012 |
ISSN: | 0028-0836 1476-4687 |
Statement of Responsibility: | Jian Yang ... Lyle J. Palmer ... et al. |
Abstract: | There is evidence across several species for genetic control of phenotypic variation of complex traits1–4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at theFTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5–7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at theFTO locus is approximately 7%, corresponding to a difference of 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9,10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000. |
Keywords: | Humans Proteins Nerve Tissue Proteins Repressor Proteins Body Mass Index Body Height Phenotype Polymorphism, Single Nucleotide Female Male Genetic Variation Genome-Wide Association Study Co-Repressor Proteins Alpha-Ketoglutarate-Dependent Dioxygenase FTO |
DOI: | 10.1038/nature11401 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/241944 http://purl.org/au-research/grants/nhmrc/389875 http://purl.org/au-research/grants/nhmrc/389891 http://purl.org/au-research/grants/nhmrc/389892 http://purl.org/au-research/grants/nhmrc/389938 http://purl.org/au-research/grants/nhmrc/442915 http://purl.org/au-research/grants/nhmrc/442981 http://purl.org/au-research/grants/nhmrc/496739 http://purl.org/au-research/grants/nhmrc/496688 http://purl.org/au-research/grants/nhmrc/552485 http://purl.org/au-research/grants/nhmrc/613672 http://purl.org/au-research/grants/nhmrc/613601 http://purl.org/au-research/grants/nhmrc/1011506 http://purl.org/au-research/grants/arc/DP1093502 |
Published version: | http://dx.doi.org/10.1038/nature11401 |
Appears in Collections: | Aurora harvest 7 Translational Health Science publications |
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