A genome-wide association study reveals variants in ARL15 that influence adiponectin levels

Brent Richards, J., Waterworth, Dawn, O'Rahilly, Stephen, Hivert, Marie-France, Loos, Ruth J. F., Perry, John R. B., Tanaka, Toshiko, Timpson, Nicholas John, Semple, Robert K., Soranzo, Nicole, Song, Kijoung, Rocha, Nuno, Grundberg, Elin, Dupuis, Josee, Florez, Jose C., Langenberg, Claudia, Prokopenko, Inga, Saxena, Richa, Sladek, Robert, Aulchenko, Yurii, Evans, David, Waeber, Gerard, Erdmann, Jeanette, Burnett, Mary-Susan, Sattar, Naveed, Devaney, Joseph, Willenborg, Christina, Hingorani, Aroon, Witteman, Jaquelin C. M, Vollenweider, Peter, Glaser, Beate, Hengstenberg, Christian, Ferrucci, Luigi, Melzer, David, Stark, Klaus, Deanfield, John, Winogradow, Janina, Grassl, Martina, Hall, Alistair S., Egan, Josephine M., Thompson, John R., Ricketts, Sally L., Konig, Inke R., Reinhard, Wibke, Grundy, Scott, Wichmann, H-Erich, Barter, Phil, Mahley, Robert, Kesaniemi, Y. Antero, Rader, Daniel J., Reilly,Muredach P., Epstein, Stephen E., Stewart, Alexandre F. R., Van Duijn, Cornelia M., Schunkert, Heribert, Burling, Keith, Deloukas, Panos, Pastinen, Tomi, Samani, Nilesh J., McPherson, Ruth, Smith, George Davey, Frayling, Timothy M., Wareham, Nicholas J., Meigs, James B., Mooser, Vincent and Spector, Tim D. (2009) A genome-wide association study reveals variants in ARL15 that influence adiponectin levels. PLoS Genetics, 5 12: e1000768.1-e1000768.10. doi:10.1371/journal.pgen.1000768


Author Brent Richards, J.
Waterworth, Dawn
O'Rahilly, Stephen
Hivert, Marie-France
Loos, Ruth J. F.
Perry, John R. B.
Tanaka, Toshiko
Timpson, Nicholas John
Semple, Robert K.
Soranzo, Nicole
Song, Kijoung
Rocha, Nuno
Grundberg, Elin
Dupuis, Josee
Florez, Jose C.
Langenberg, Claudia
Prokopenko, Inga
Saxena, Richa
Sladek, Robert
Aulchenko, Yurii
Evans, David
Waeber, Gerard
Erdmann, Jeanette
Burnett, Mary-Susan
Sattar, Naveed
Devaney, Joseph
Willenborg, Christina
Hingorani, Aroon
Witteman, Jaquelin C. M
Vollenweider, Peter
Glaser, Beate
Hengstenberg, Christian
Ferrucci, Luigi
Melzer, David
Stark, Klaus
Deanfield, John
Winogradow, Janina
Grassl, Martina
Hall, Alistair S.
Egan, Josephine M.
Thompson, John R.
Ricketts, Sally L.
Konig, Inke R.
Reinhard, Wibke
Grundy, Scott
Wichmann, H-Erich
Barter, Phil
Mahley, Robert
Kesaniemi, Y. Antero
Rader, Daniel J.
Reilly,Muredach P.
Epstein, Stephen E.
Stewart, Alexandre F. R.
Van Duijn, Cornelia M.
Schunkert, Heribert
Burling, Keith
Deloukas, Panos
Pastinen, Tomi
Samani, Nilesh J.
McPherson, Ruth
Smith, George Davey
Frayling, Timothy M.
Wareham, Nicholas J.
Meigs, James B.
Mooser, Vincent
Spector, Tim D.
Title A genome-wide association study reveals variants in ARL15 that influence adiponectin levels
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2009
Year available 2009
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1000768
Open Access Status DOI
Volume 5
Issue 12
Start page e1000768.1
End page e1000768.10
Total pages 10
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2010
Language eng
Subject 1311 Genetics
1312 Molecular Biology
1105 Dentistry
1306 Cancer Research
2716 Genetics (clinical)
Abstract The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P≤5×10-8). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P≤0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2×10-19 for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9×10-8, n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5×10-6, n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2×10-3, n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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