FTO genotype is associated with phenotypic variability of body mass index

Yang, Jian, Loos, Ruth J.F., Powell, Joseph E., Medland, Sarah E., Speliotes, Elizabeth K., Chasman, Daniel I., Rose, Lynda M., Thorleifsson, Gudmar, Steinthorsdottir, Valgerdur, Mägi, Reedik, Waite, Lindsay, Vernon Smith, Albert, Yerges-Armstrong, Laura M., Monda, Keri L., Hadley, David, Mahajan, Anubha, Li, Guo, Kapur, Karen, Vitart, Veronique, Huffman, Jennifer E., Wang, Sophie R., Palmer, Cameron, Esko, Tõnu, Fischer, Krista, Hua Zhao, Jing, Demirkan, Ayşe, Isaacs, Aaron, Feitosa, Mary F., Luan, Jian’an, Heard-Costa, Nancy L., White, Charles, Jackson, Anne U., Preuss, Michael, Ziegler, Andreas, Eriksson, Joel, Kutalik, Zoltán, Frau, Francesca, Nolte, Ilja M., Van Vliet-Ostaptchouk, Jana V., Hottenga, Jouke-Jan, Jacobs, Kevin B., Verweij, Niek, Goel, Anuj, Medina-Gomez, Carolina, Estrada, Karol, Lynn Bragg-Gresham, Jennifer, Sanna, Serena, Sidore, Carlo, Tyrer, Jonathan, Teumer, Alexander, Prokopenko, Inga, Mangino, Massimo, Lindgren, Cecilia M., Assimes, Themistocles L., Shuldiner, Alan R., Hui, Jennie, Beilby, John P., McArdle, Wendy L., Hall, Per, Haritunians, Talin, Zgaga, Lina, Kolcic, Ivana, Polasek, Ozren, Zemunik, Tatijana, Oostra, Ben A., Juhani Junttila, M., Grönberg, Henrik, Schreiber, Stefan, Peters, Annette, Hicks, Andrew A., Stephens, Jonathan, Foad, Nicola S., Laitinen, Jaana, Pouta, Anneli, Kaakinen, Marika, Willemsen, Gonneke, Vink, Jacqueline M., Wild, Sarah H., Navis, Gerjan, Asselbergs, Folkert W., Homuth, Georg, John, Ulrich, Iribarren, Carlos, Harris, Tamara, Launer, Lenore, Gudnason, Vilmundur, O’Connell, Jeffrey R., Boerwinkle, Eric, Cadby, Gemma, Palmer, Lyle J., James, Alan L., Musk, Arthur W., Ingelsson, Erik, Psaty, Bruce M., Beckmann, Jacques S., Waeber, Gerard, Vollenweider, Peter, Hayward, Caroline, Wright, Alan F., Rudan, Igor, Groop, Leif C., Metspalu, Andres, Tee Khaw, Kay, van Duijn, Cornelia M., Borecki, Ingrid B., Province, Michael A., Wareham, Nicholas J., Tardif, Jean-Claude, Huikuri, Heikki V., Adrienne Cupples, L., Atwood, Larry D., Fox, Caroline S., Boehnke, Michael, Collins, Francis S., Mohlke, Karen L., Erdmann, Jeanette, Schunkert, Heribert, Hengstenberg, Christian, Stark, Klaus, Lorentzon, Mattias, Ohlsson, Claes, Cusi, Daniele, Staessen, Jan A., Van der Klauw, Melanie M., Pramstaller, Peter P., Kathiresan, Sekar, Jolley, Jennifer D., Ripatti, Samuli, Jarvelin, Marjo-Riitta, de Geus, Eco J. C., Boomsma, Dorret I., Penninx, Brenda, Wilson, James F., Campbell, Harry, Chanock, Stephen J., van der Harst, Pim, Hamsten, Anders, Watkins, Hugh, Hofman, Albert, Witteman, Jacqueline C., Zillikens, M. Carola, Uitterlinden, André G., Rivadeneira, Fernando, Carola Zillikens, M., Kiemeney, Lambertus A., Vermeulen, Sita H., Abecasis, Goncalo R., Schlessinger, David, Schipf, Sabine, Stumvoll, Michael, Tönjes, Anke, Spector, Tim D., North, Kari E., Lettre, Guillaume, McCarthy, Mark I., Berndt, Sonja I., Heath, Andrew C., Madden, Pamela A. F., Nyholt, Dale R., Montgomery, Grant W., Martin, Nicholas G., McKnight, Barbara, Strachan, David P., Hill, William G., Snieder, Harold, Ridker, Paul M., Thorsteinsdottir, Unnur, Stefansson, Kari, Frayling, Timothy M., Hirschhorn, Joel N., Goddard, Michael E., & Visscher, Peter M. (2012) FTO genotype is associated with phenotypic variability of body mass index. Nature, 490(7419), pp. 267-272.

View at publisher


There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 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 the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 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 the FTO 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.

Impact and interest:

142 citations in Scopus
126 citations in Web of Science®
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 91878
Item Type: Journal Article
Refereed: Yes
Keywords: Genetics, Health and medicine, Genomics
DOI: 10.1038/nature11401
ISSN: 1476-4687
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 14 Jan 2016 01:05
Last Modified: 26 Jun 2017 19:01

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page