Please use this identifier to cite or link to this item: http://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
RMID: 0020136604
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
Appears in Collections:Translational Health Science publications

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