198-LB: Pleiotropy Analysis of Adiposity, Glycemic, and Renal Traits in the Population Architecture Using Genomics in Epidemiology (PAGE) Consortium

A shared genetic susceptibility underlies diabetes, adiposity, and kidney phenotypes, yet few studies have leveraged this common genetic architecture in an attempt to clarify molecular functions, identify mechanistic common denominators, and prioritize variants for functional interrogation. We systematically interrogated evidence of a shared genetic architecture across adiposity (BMI [N=90,813], waist circumference[N=68,389], and waist to hip ratio [WHR, N=63,747]), type 2 diabetes (T2D, [N=98,686, Ncase=26,440], fasting glucose [FG, N=52,211], HbA1c [N=23,357], and fasting insulin [FI, N=48,395]), and kidney (eGFR [N=52,555] and chronic kidney disease [CKD, N=91,382, Ncase=10,883]) phenotypes in an ancestrally diverse study population (28% African American, 31% European ancestry, 28% Hispanic; 69% female; average age 56.9 (range 18-90)) within PAGE. We conducted a cross-trait meta-analysis using Adaptive Sum of Powered Score Tests (aSPU). We have identified 42 loci associated across these traits, (P Disclosure H.M. Highland: None. C. Downie: None. S.F. Dimos: None. M. Graff: None. L.M. Polfus: None. B.F. Darst: None. A.R.M. Baldassari: None. C. Sitlani: None. A. Howard: None. C.L. Kooperberg: None. R. Loos: None. T. Matise: None. A.K. Mottl: None. K.E. North: None. C.L. Avery: Research Support; Self; Amgen. Funding American Diabetes Association (1-19-PDF-045 to H.M.M.); National Institutes of Health (T32HL007055, T32HL129982, R01HL142825)