title: KIR genotypic diversity can track ancestries in heterogeneous populations: a potential confounder for disease association studies.
abstract: Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this, we characterized the diversity of 16 KIR genes in 712 Northern Californians (NC) stratified by self-assigned ethnicities and compared the profiles of KIR polymorphism with other US and global populations using a reference database. Sixty-eight distinct KIR genotypes were characterized: 58 in 457 Caucasians (NCC), 17 in 47 African Americans (NCAA), 21 in 80 Asians (NCA), 20 in 74 Hispanics (NCH), and 18 in 54 "other" ethnicities (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were compared with each other and with 34 global populations by phylogenetic analysis. Although there were no population-specific genotypes, the KIR genotype frequency patterns faithfully traced the ancestry of NCC, NCAA, and NCA but not of NCH whose ancestries are known to be more heterogeneous. KIR genotype frequencies can therefore track ethnic ancestries in modern urban populations. Our data emphasize the importance of selecting ethnically matched controls in KIR-based studies to avert spurious associations.
authors: Kalmanovitz Liver Immunology Laboratory, California Pacific Medical Center & Research Institute, 2340 Clay Street, 3rd floor, San Francisco, CA 94115, USA.
authors: Komal Manpreet
authors: KM
authors: Singh
authors: Yume T
authors: YT
authors: Phung
authors: Mohamed S
authors: MS
authors: Kohla
authors: Billy Y-A
authors: BY
authors: Lan
authors: Sharon
authors: S
authors: Chan
authors: Diana L
authors: DL
authors: Suen
authors: Sahar
authors: S
authors: Murad
authors: Shana
authors: S
authors: Rheault
authors: Peter
authors: P
authors: Davidson
authors: Jennifer
authors: J
authors: Evans
authors: Manpreet
authors: M
authors: Singh
authors: Sofie
authors: S
authors: Dohil
authors: Robert W
authors: RW
authors: Osorio
authors: Adil E
authors: AE
authors: Wakil
authors: Kimberly
authors: K
authors: Page
authors: Sandy
authors: S
authors: Feng
authors: Stewart L
authors: SL
authors: Cooper
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002140:California; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods*; D006239:Haplotypes; D006801:Humans; D010802:Phylogeny; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics*; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D054340:Receptors, KIR