A1 Refereed original research article in a scientific journal
Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology
Authors: Spracklen CN, Karaderi T, Yaghootkar H, Schurmann C, Fine RS, Kutalik Z, Preuss MH, Lu YC, Wittemans LBL, Adair LS, Allison M, Amin N, Auer PL, Bartz TM, Bluher M, Boehnke M, Borja JB, Bork-Jensen J, Broer L, Chasman DI, Chen YDI, Chirstofidou P, Demirkan A, van Duijn CM, Feitosa MF, Garcia ME, Graff M, Grallert H, Grarup N, Guo XQ, Haesser J, Hansen T, Harris TB, Highland HM, Hong J, Ikram MA, Ingelsson E, Jackson R, Jousilahti P, Kahonen M, Kizer JR, Kovacs P, Kriebel J, Laakso M, Lange LA, Lehtimaki T, Li J, Ruifang LG, Lind L, Luan JA, Lyytikainen LP, MacGregor S, Mackey DA, Mahajan A, Mangino M, Mannisto S, McCarthy MI, McKnight B, Medina-Gomez C, Meigs JB, Molnos S, Mook-Kanamori D, Morris AP, de Mutsert R, Nalls MA, Nedeljkovic I, North KE, Pennell CE, Pradhan AD, Province MA, Raitakari OT, Raulerson CK, Reiner AP, Ridker PM, Ripatti S, Roberston N, Rotter JI, Salomaa V, Sandoval-Zarate AA, Sitlani CM, Spector TD, Strauch K, Stumvoll M, Taylor KD, Thuesen B, Tonjes A, Uitterlinden AG, Venturini C, Walker M, Wang CA, Wang S, Wareham NJ, Willems SM, van Dijk KW, Wilson JG, Wu Y, Yao J, Young KL, Langenberg C, Frayling TM, Kilpelainen TO, Lindgren CM, Loos RJF, Mohlke KL
Publisher: CELL PRESS
Publication year: 2019
Journal: American Journal of Human Genetics
Journal name in source: AMERICAN JOURNAL OF HUMAN GENETICS
Journal acronym: AM J HUM GENET
Volume: 105
Issue: 1
First page : 15
Last page: 28
Number of pages: 14
ISSN: 0002-9297
eISSN: 1537-6605
DOI: https://doi.org/10.1016/j.ajhg.2019.05.002
Self-archived copy’s web address: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612516/
Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 x 10(-7)). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r(2) > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.
