PMID- 34976003
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220104
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 12
DP  - 2021
TI  - STXBP6 and B3GNT6 Genes are Associated With Selective IgA Deficiency.
PG  - 736235
LID - 10.3389/fgene.2021.736235 [doi]
LID - 736235
AB  - Immunoglobulin A Deficiency (IgAD) is a polygenic primary immune deficiency, with 
      a strong genetic association to the human leukocyte antigen (HLA) region. 
      Previous genome-wide association studies (GWAS) have identified five non-HLA risk 
      loci (IFIH1, PVT1, ATG13-AMBRA1, AHI1 and CLEC16A). In this study, we 
      investigated the genetic interactions between different HLA susceptibility 
      haplotypes and non-MHC genes in IgAD. To do this, we stratified IgAD subjects and 
      healthy controls based on HLA haplotypes (N = 10,993), and then performed GWAS to 
      identify novel genetic regions contributing to IgAD susceptibility. After 
      replicating previously published HLA risk haplotypes, we compared individuals 
      carrying at least one HLA risk allele (HLA-B*08:01-DRB1*03:01-DQB1*02:01 or 
      HLA-DRB1*07:01-DQB1*02:02 or HLA-DRB1*01-DQB1*05:01) with individuals lacking an 
      HLA risk allele. Subsequently, we stratified subjects based on the susceptibility 
      alleles/haplotypes and performed gene-based association analysis using 572,856 
      SNPs and 24,125 genes. A significant genome-wide association in STXBP6 
      (rs4097492; p = 7.63 x 10(-9)) was observed in the cohort carrying at least one 
      MHC risk allele. We also identified a significant gene-based association for 
      B3GNT6 (P (Gene) = 2.1 x 10(-6)) in patients not carrying known HLA 
      susceptibility alleles. Our findings indicate that the etiology of IgAD differs 
      depending on the genetic background of HLA susceptibility haplotypes.
CI  - Copyright (c) 2021 Lim, Bronson, Varade, Behrens and Hammarstrom.
FAU - Lim, Che Kang
AU  - Lim CK
AD  - Department of Laboratory Medicine, Karolinska Institutet, Karolinska University, 
      Hospital Huddinge, Stockholm, Sweden.
AD  - Department Clinical Translation Research, Singapore General Hospital, Singapore, 
      Singapore.
FAU - Bronson, Paola G
AU  - Bronson PG
AD  - RED OMNI Human Genetics, Genentech, South San Francisco, CA, United States.
FAU - Varade, Jezabel
AU  - Varade J
AD  - Department of Laboratory Medicine, Karolinska Institutet, Karolinska University, 
      Hospital Huddinge, Stockholm, Sweden.
AD  - Biomedical Research Center (CINBIO) Singular Research Center, University of Vigo, 
      Vigo, Spain.
FAU - Behrens, Timothy W
AU  - Behrens TW
AD  - Maze Therapeutics, South San Francisco, CA, United States.
FAU - Hammarstrom, Lennart
AU  - Hammarstrom L
AD  - Department of Laboratory Medicine, Karolinska Institutet, Karolinska University, 
      Hospital Huddinge, Stockholm, Sweden.
AD  - Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
AD  - BGI-Shenzhen, Shenzhen, China.
LA  - eng
PT  - Journal Article
DEP - 20211217
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC8718598
OTO - NOTNLM
OT  - HLA risk allele
OT  - Stratification
OT  - immunoglobulin a deficiency
OT  - major histocompatibility complex (MHC)
OT  - non-MHC genes
COIS- PB was employed by RED OMNI Human Genetics, Genentech; TB was employed by Maze 
      Therapeutics. The remaining authors declare that the research was conducted in 
      the absence of any commercial or financial relationships that could be construed 
      as a potential conflict of interest. The remaining authors declare that the 
      research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest. The 
      handling editor declared a past co-authorship with one of the authors (LH).
EDAT- 2022/01/04 06:00
MHDA- 2022/01/04 06:01
PMCR- 2021/12/17
CRDT- 2022/01/03 05:39
PHST- 2021/07/04 00:00 [received]
PHST- 2021/11/11 00:00 [accepted]
PHST- 2022/01/03 05:39 [entrez]
PHST- 2022/01/04 06:00 [pubmed]
PHST- 2022/01/04 06:01 [medline]
PHST- 2021/12/17 00:00 [pmc-release]
AID - 736235 [pii]
AID - 10.3389/fgene.2021.736235 [doi]
PST - epublish
SO  - Front Genet. 2021 Dec 17;12:736235. doi: 10.3389/fgene.2021.736235. eCollection 
      2021.