Journal
HUMAN MOLECULAR GENETICS
Volume 23, Issue 4, Pages 1108-1119Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt488
Keywords
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Funding
- Biomedical Research Council [03/1/27/18/216]
- National Medical Research Council [0838/2004, NMRC/CSI/0002/2005]
- Seoul R&BD program, Republic of Korea [10526]
- National R&D Program for Cancer Control
- Ministry for Health, Welfare and Family Affairs, Republic of Korea [0920330, 1220180, A000385]
- National Research Foundation of Korea (NRF)
- Korea government (MEST) [2011-0029348]
- National Institutes of Health [DK078150, TW005596, HL085144, R01 CA082729]
- pilot [RR020649, ES010126, DK056350]
- National High Technology Research and Development Program [2009AA022704]
- Knowledge Innovation Program [KSCX2-EW-R-10]
- National Natural Science Foundation of China [30930081, 81021002, 81170734]
- National Key Basic Research Program of China [2012CB524900]
- Korea Centers for Disease Control and Prevention [2007-E71001-00, 2008-E71001-00]
- Korea Healthcare Technology RD Project
- Japan Society for the Promotion of Science [17209021, 21390209]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [1601223, 17019028, 18018020, 20018026]
- National Science Council of Taiwan [NSC94-3112-B-002-019, NSC95-3112-B-002-002, NSC96-3112-B-002-002]
- National Health Research Institutes (NHRI) in Taiwan [EC0950806, N06213, 200701083R, 95-11-20A, BS-092(similar to097)-PP-01, PH-98(similar to102)-PP03, PH-98(similar to102)-PP04]
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Science and Technology Incubation Program in Advanced Regions from the Japan Science and Technology Agency
- Japan Arteriosclerosis Prevention Fund
- Research Promotion Award of Ehime University
- Grants-in-Aid for Scientific Research [21390209, 17019028, 18018020, 25893087, 24390084, 20018026, 17209021, 24390169] Funding Source: KAKEN
- National Research Foundation of Korea [2011-0029348] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P 3.0 10(14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P 1.2 10(7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P 6.8 10(165)), ADIPOQ (P 1.8 10(22)), PEPD (P 3.6 10(12)), CMIP (P 2.1 10(10)), ZNF664 (P 2.3 10(7)) and GPR109A (P 7.4 10(6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (P-initial 0.020; P-conditional 7.0 10(7)). We further confirmed the independence of two pairs of closely located loci (2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P 3.3 10(4)), high density lipoprotein cholesterol (HDL-C, P 4.9 10(4)) and body mass index (BMI)-adjusted waisthip ratio (P 9.8 10(3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.
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