Please use this identifier to cite or link to this item:
Title: Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico
Authors: Williams Amy, A.L.
Jacobs Suzanne, S.B.R.
Moreno-Macías, H.
Huerta-Chagoya, A.
Churchhouse, C.
Márquez-Luna, C.
Gómez-Vázquez, M.J.
Burtt Noël, N.P.
Aguilar-Salinas, C.A.
González-Villalpando, C.
Florez, J.C.
Orozco, L.
Tusié-Luna, T.
Altshuler, D.
Ripke, S.
Manning, A.K.
García-Ortíz, H.
Neale, B.
Reich, D.
Stram, D.O.
Fernández-López, J.C.
Romero-Hidalgo, S.
Patterson, N.
Haiman, C.A.
Aguilar-Delfín, I.
Martínez-Hernández, A.
Centeno-Cruz, F.
Mendoza-Caamal, E.
Revilla-Monsalve, C.
Islas-Andrade, S.
Córdova, E.
Rodríguez-Arellano, E.
Soberón, X.
Florez Jose, J.C.
González-Villalpando María Elena, M.A.
Henderson, B.E.
Monroe, K.
Wilkens, L.
Kolonel, L.N.
Le Marchand, L.
Riba, L.
Ordóñez-Sánchez María Luisa, M.A.
Rodríguez-Guillén, R.
Cruz-Bautista, I.
Rodríguez-Torres, M.
Muñoz-Hernández, L.L.
Sáenz, T.
Gómez, D.
Alvirde, U.
Onofrio, R.C.
Brodeur, W.M.
Gage, D.
Murphy, J.
Franklin, J.
Mahan, S.
Ardlie, K.
Crenshaw, A.T.
Winckler, W.
Prüfer, K.
Shunkov, M.V.
Sawyer, S.
Stenzel, U.
Kelso, J.
Lek, M.
Sankararaman, S.
MacArthur, D.G.
Derevianko, A.P.
Pääbo, S.
Jacobs, S.B.R.
Gopal, S.
Grammatikos, J.A.
Smith, I.C.
Bullock, K.H.
Deik, A.A.
Souza, A.L.
Pierce, K.A.
Clish, C.B.
Fennell, T.
Farjoun, Y.
Gabriel, S.
Gross, M.D.
Pereira, M.A.
Seielstad, M.
Koh, W.-P. 
Tai, E.-S.
Flannick, J.
Fontanillas, P.
Morris, A.
Teslovich, T.M.
Atzmon, G.
Blangero, J.
Bowden, D.W.
Chambers, J.
Cho, Y.S.
Duggirala, R.
Glaser, B.
Hanis, C.
Kooner, J.
Laakso, M.
Lee, J.-Y.
Teo, Y.Y.
Wilson, J.G.
Puppala, S.
Farook, V.S.
Thameem, F.
Abboud, H.E.
DeFronzo, R.A.
Jenkinson, C.P.
Lehman, D.M.
Curran, J.E.
Cortes, M.L.
González-Villalpando Clicerio, C.
Orozco Lorena, L.
Issue Date: 2014
Citation: Williams Amy, A.L., Jacobs Suzanne, S.B.R., Moreno-Macías, H., Huerta-Chagoya, A., Churchhouse, C., Márquez-Luna, C., Gómez-Vázquez, M.J., Burtt Noël, N.P., Aguilar-Salinas, C.A., González-Villalpando, C., Florez, J.C., Orozco, L., Tusié-Luna, T., Altshuler, D., Ripke, S., Manning, A.K., García-Ortíz, H., Neale, B., Reich, D., Stram, D.O., Fernández-López, J.C., Romero-Hidalgo, S., Patterson, N., Haiman, C.A., Aguilar-Delfín, I., Martínez-Hernández, A., Centeno-Cruz, F., Mendoza-Caamal, E., Revilla-Monsalve, C., Islas-Andrade, S., Córdova, E., Rodríguez-Arellano, E., Soberón, X., Florez Jose, J.C., González-Villalpando María Elena, M.A., Henderson, B.E., Monroe, K., Wilkens, L., Kolonel, L.N., Le Marchand, L., Riba, L., Ordóñez-Sánchez María Luisa, M.A., Rodríguez-Guillén, R., Cruz-Bautista, I., Rodríguez-Torres, M., Muñoz-Hernández, L.L., Sáenz, T., Gómez, D., Alvirde, U., Onofrio, R.C., Brodeur, W.M., Gage, D., Murphy, J., Franklin, J., Mahan, S., Ardlie, K., Crenshaw, A.T., Winckler, W., Prüfer, K., Shunkov, M.V., Sawyer, S., Stenzel, U., Kelso, J., Lek, M., Sankararaman, S., MacArthur, D.G., Derevianko, A.P., Pääbo, S., Jacobs, S.B.R., Gopal, S., Grammatikos, J.A., Smith, I.C., Bullock, K.H., Deik, A.A., Souza, A.L., Pierce, K.A., Clish, C.B., Fennell, T., Farjoun, Y., Gabriel, S., Gross, M.D., Pereira, M.A., Seielstad, M., Koh, W.-P., Tai, E.-S., Flannick, J., Fontanillas, P., Morris, A., Teslovich, T.M., Atzmon, G., Blangero, J., Bowden, D.W., Chambers, J., Cho, Y.S., Duggirala, R., Glaser, B., Hanis, C., Kooner, J., Laakso, M., Lee, J.-Y., Teo, Y.Y., Wilson, J.G., Puppala, S., Farook, V.S., Thameem, F., Abboud, H.E., DeFronzo, R.A., Jenkinson, C.P., Lehman, D.M., Curran, J.E., Cortes, M.L., González-Villalpando Clicerio, C., Orozco Lorena, L. (2014). Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature 506 (7486) : 97-101. ScholarBank@NUS Repository.
Abstract: Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 × 10-13; odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 × 10-4; OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ∼50% frequency in Native American samples and ∼10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism. © 2014 Macmillan Publishers Limited. All rights reserved.
Source Title: Nature
ISSN: 00280836
DOI: 10.1038/nature12828
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.