Admixture Mapping in Lupus Identifies Multiple Functional Variants within IFIH1 Associated with Apoptosis, Inflammation, and Autoantibody Production
Julio Molineros;Amit Maiti;Celi Sun;Loren Looger;Shizhong Han;Xana Kim-Howard;Stuart Glenn;Adam Adler;Jennifer Kelly;Timothy Niewold;Gary Gilkeson;Elizabeth Brown;Graciela S. Alarcón;Jeffrey Edberg;Michelle Petri;Rosalind Ramsey-Goldman;John Reveille;Luis M. Vilá;Barry Freedman;Betty Tsao;Lindsey Criswell;Chaim Jacob;Jason Moore;Timothy Vyse;Carl Langefeld;Joel Guthridge;Patrick Gaffney;Kathy Moser;R. Hal Scofield;Marta E. Alarcón-Riquelme;on behalf of the BIOLUPUS Network;Scott Williams;Joan Merrill;Judith James;Kenneth Kaufman;Robert Kimberly;John Harley;Swapan Nath
Abstract
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with a strong genetic component. African-Americans (AA) are at increased risk of SLE, but the genetic basis of this risk is largely unknown. To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA). Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22–24 (LOD = 6.28), and the admixture signal is