PMID- 36777335
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230214
IS  - 2666-979X (Electronic)
IS  - 2666-979X (Linking)
VI  - 2
IP  - 3
DP  - 2022 Mar 9
TI  - Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing 
      and a high-resolution imputation method.
PG  - 100101
LID - 10.1016/j.xgen.2022.100101 [doi]
LID - 100101
AB  - The killer cell immunoglobulin-like receptor (KIR) recognizes human leukocyte 
      antigen (HLA) class I molecules and modulates the function of natural killer 
      cells. Despite its role in immunity, the complex genomic structure has limited a 
      deep understanding of the KIR genomic landscape. Here we conduct deep sequencing 
      of 16 KIR genes in 1,173 individuals. We devise a bioinformatics pipeline 
      incorporating copy number estimation and insertion or deletion (indel) calling 
      for high-resolution KIR genotyping. We define 118 alleles in 13 genes and 
      demonstrate a linkage disequilibrium structure within and across KIR centromeric 
      and telomeric regions. We construct a KIR imputation reference panel 
      (n(reference) = 689, imputation accuracy = 99.7%), apply it to biobank genotype 
      (n(total) = 169,907), and perform phenome-wide association studies of 85 traits. 
      We observe a dearth of genome-wide significant associations, even in immune 
      traits implicated previously to be associated with KIR (the smallest p = 1.5 x 
      10(-4)). Our pipeline presents a broadly applicable framework to evaluate innate 
      immunity in large-scale datasets.
CI  - (c) 2022 The Author(s).
FAU - Sakaue, Saori
AU  - Sakaue S
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
AD  - Center for Data Sciences, Harvard Medical School, Boston, MA 02115, USA.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA 02142, USA.
AD  - Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Hosomichi, Kazuyoshi
AU  - Hosomichi K
AD  - Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive 
      Medical Sciences, Kanazawa University, Ishikawa 920-8640, Japan.
FAU - Hirata, Jun
AU  - Hirata J
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Nakaoka, Hirofumi
AU  - Nakaoka H
AD  - Human Genetics Laboratory, National Institute of Genetics, Shizuoka 411-8540, 
      Japan.
FAU - Yamazaki, Keiko
AU  - Yamazaki K
AD  - Laboratory for Genotyping Development, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
AD  - Department of Public Health, Graduate School of Medicine, Chiba University, Chiba 
      260-8670, Japan.
AD  - Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Yawata, Makoto
AU  - Yawata M
AD  - Department of Paediatrics, Yong Loo Lin School of Medicine, National University 
      of Singapore, and National University Health System, Singapore 119228, Singapore.
AD  - NUSMed Immunology Translational Research Programme, and Immunology Programme, 
      Life Sciences Institute, National University of Singapore, Singapore 117456, 
      Singapore.
AD  - Singapore Institute for Clinical Sciences, Agency for Science, Technology and 
      Research, Singapore 117609, Singapore.
AD  - International Research Center for Medical Sciences, Kumamoto University, Kumamoto 
      860-0811, Japan.
FAU - Yawata, Nobuyo
AU  - Yawata N
AD  - Department of Ocular Pathology and Imaging Science, Kyushu University, 812-8582, 
      Japan.
AD  - Singapore Eye Research Institute, Singapore 169856, Singapore.
AD  - Duke-NUS Medical School, Singapore 169857, Singapore.
FAU - Naito, Tatsuhiko
AU  - Naito T
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
AD  - Department of Neurology, Graduate School of Medicine, The University of Tokyo, 
      Tokyo 113-8655, Japan.
FAU - Umeno, Junji
AU  - Umeno J
AD  - Department of Medicine and Clinical Science, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka 812-8582, Japan.
FAU - Kawaguchi, Takaaki
AU  - Kawaguchi T
AD  - Division of Gastroenterology, Department of Medicine, Tokyo Yamate Medical 
      Center, Tokyo 169-0073, Japan.
FAU - Matsui, Toshiyuki
AU  - Matsui T
AD  - Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka 
      818-0067, Japan.
FAU - Motoya, Satoshi
AU  - Motoya S
AD  - Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo 060-0033, 
      Japan.
FAU - Suzuki, Yasuo
AU  - Suzuki Y
AD  - Department of Internal Medicine, Faculty of Medicine, Toho University, Chiba 
      274-8510, Japan.
FAU - Inoko, Hidetoshi
AU  - Inoko H
AD  - GenoDive Pharma Inc., Atsugi 243-0018, Japan.
FAU - Tajima, Atsushi
AU  - Tajima A
AD  - Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive 
      Medical Sciences, Kanazawa University, Ishikawa 920-8640, Japan.
FAU - Morisaki, Takayuki
AU  - Morisaki T
AD  - Division of Molecular Pathology, The Institute of Medical Science, The University 
      of Tokyo, Tokyo 108-8639, Japan.
FAU - Matsuda, Koichi
AU  - Matsuda K
AD  - Department of Computational Biology and Medical Sciences, Graduate School of 
      Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan.
FAU - Kamatani, Yoichiro
AU  - Kamatani Y
AD  - Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
AD  - Laboratory of Complex Trait Genomics, Department of Computational Biology and 
      Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 
      Tokyo 108-8639, Japan.
FAU - Yamamoto, Kazuhiko
AU  - Yamamoto K
AD  - Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical 
      Sciences, Yokohama 230-0045, Japan.
FAU - Inoue, Ituro
AU  - Inoue I
AD  - Human Genetics Laboratory, National Institute of Genetics, Shizuoka 411-8540, 
      Japan.
FAU - Okada, Yukinori
AU  - Okada Y
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
AD  - Laboratory of Statistical Immunology, Immunology Frontier Research Center 
      (WPI-IFReC), Osaka University, Suita 565-0871, Japan.
AD  - Integrated Frontier Research for Medical Science Division, Institute for Open and 
      Transdisciplinary Research Initiatives, Osaka University, Suita 565-0871, Japan.
AD  - Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, 
      Yokohama 230-0045, Japan.
AD  - Center for Infectious Disease Education and Research (CiDER), Osaka University, 
      Suita 565-0871, Japan.
LA  - eng
PT  - Journal Article
DEP - 20220309
PL  - United States
TA  - Cell Genom
JT  - Cell genomics
JID - 9918284260106676
PMC - PMC9903714
OTO - NOTNLM
OT  - KIR
OT  - PheWAS
OT  - biobank
OT  - immunogenetics
OT  - imputation
OT  - killer cell immunoglobulin-like receptor
OT  - next-generation sequencing
OT  - target sequencing
COIS- H.I. is a founder of GenoDive Pharma. Inc. J.H. is an employee of Teijin Pharma 
      Limited.
EDAT- 2023/02/14 06:00
MHDA- 2023/02/14 06:01
PMCR- 2022/03/09
CRDT- 2023/02/13 03:34
PHST- 2021/01/15 00:00 [received]
PHST- 2021/08/07 00:00 [revised]
PHST- 2022/02/02 00:00 [accepted]
PHST- 2023/02/13 03:34 [entrez]
PHST- 2023/02/14 06:00 [pubmed]
PHST- 2023/02/14 06:01 [medline]
PHST- 2022/03/09 00:00 [pmc-release]
AID - S2666-979X(22)00018-0 [pii]
AID - 100101 [pii]
AID - 10.1016/j.xgen.2022.100101 [doi]
PST - epublish
SO  - Cell Genom. 2022 Mar 9;2(3):100101. doi: 10.1016/j.xgen.2022.100101. eCollection 
      2022 Mar 9.