{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang YN"],"funding":["Natural Science Foundation of Beijing Municipality","Peking University","Chinese Academy of Medical Sciences","Beijing Nova Program","Beijing Youth Top-notch Talent Support Program","National Natural Science Foundation of China","Fok Ying Tung Education Foundation"],"pagination":["545-552"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7920185"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(3)"],"pubmed_abstract":["<h4>Background</h4>Galactose-deficient IgA1 plays a key role in the pathogenesis of IgA nephropathy, the most common primary GN worldwide. Although serum levels of galactose-deficient IgA1 have a strong genetic component, the genetic link between this molecule and IgA nephropathy has not yet been clearly established.<h4>Methods</h4>To identify novel loci associated with galactose-deficient IgA1, we performed a quantitative genome-wide association study for serum galactose-deficient IgA1 levels, on the basis of two different genome-wide association study panels conducted in 1127 patients with IgA nephropathy. To test genetic associations with susceptibility to IgA nephropathy, we also enrolled 2352 patients with biopsy-diagnosed IgA nephropathy and 2632 healthy controls. Peripheral blood samples from 59 patients and 27 healthy controls were also collected for gene expression analysis.<h4>Results</h4>We discovered two loci, in <i>C1GALT1</i> and <i>GALNT12,</i> that achieved genome-wide significance, explaining about 3.7% and 3.4% of variance in serum galactose-deficient IgA1 levels, respectively. We confirmed the previously reported association of <i>C1GALT1</i> with serum galactose-deficient IgA1 levels, but with a different lead single-nucleotide polymorphism (rs10238682; β=0.26, <i>P</i>=1.20×10<sup>-9</sup>); the locus we identified at <i>GALNT12</i> (rs7856182; β=0.73, <i>P</i>=2.38×10<sup>-9</sup>) was novel. Of more interest, we found that <i>GALNT12</i> exhibits genetic interactions with <i>C1GALT1</i> in both galactose-deficient IgA1 levels (<i>P</i>=1.40×10<sup>-2</sup>) and disease risk (<i>P</i>=6.55×10<sup>-3</sup>). <i>GALNT12</i> mRNA expression in patients with IgA nephropathy was significantly lower compared with healthy controls.<h4>Conclusions</h4>Our data identify <i>GALNT12</i> as a novel gene associated with galactose-deficient IgA1 and suggest novel genetic interactions. These findings support a key role of genetically conferred dysregulation of galactose-deficient IgA1 in the development of IgA nephropathy."],"journal":["Journal of the American Society of Nephrology : JASN"],"pubmed_title":["Interaction between <i>G</i><i>ALNT12</i> and <i>C1GALT1</i> Associates with Galactose-Deficient IgA1 and IgA Nephropathy."],"pmcid":["PMC7920185"],"funding_grant_id":["2017000021223ZK31","PKU2020LCXQ003","82022010","Z191100001119004","82070733","171030","81970613","Z190023","2019RU023"],"pubmed_authors":["Wang YN","Chen P","Shi SF","Zhou XJ","Hou P","Zhang X","Zhang H","Lv JC","Liu LJ","Yu GZ"],"additional_accession":[]},"is_claimable":false,"name":"Interaction between <i>G</i><i>ALNT12</i> and <i>C1GALT1</i> Associates with Galactose-Deficient IgA1 and IgA Nephropathy.","description":"<h4>Background</h4>Galactose-deficient IgA1 plays a key role in the pathogenesis of IgA nephropathy, the most common primary GN worldwide. Although serum levels of galactose-deficient IgA1 have a strong genetic component, the genetic link between this molecule and IgA nephropathy has not yet been clearly established.<h4>Methods</h4>To identify novel loci associated with galactose-deficient IgA1, we performed a quantitative genome-wide association study for serum galactose-deficient IgA1 levels, on the basis of two different genome-wide association study panels conducted in 1127 patients with IgA nephropathy. To test genetic associations with susceptibility to IgA nephropathy, we also enrolled 2352 patients with biopsy-diagnosed IgA nephropathy and 2632 healthy controls. Peripheral blood samples from 59 patients and 27 healthy controls were also collected for gene expression analysis.<h4>Results</h4>We discovered two loci, in <i>C1GALT1</i> and <i>GALNT12,</i> that achieved genome-wide significance, explaining about 3.7% and 3.4% of variance in serum galactose-deficient IgA1 levels, respectively. We confirmed the previously reported association of <i>C1GALT1</i> with serum galactose-deficient IgA1 levels, but with a different lead single-nucleotide polymorphism (rs10238682; β=0.26, <i>P</i>=1.20×10<sup>-9</sup>); the locus we identified at <i>GALNT12</i> (rs7856182; β=0.73, <i>P</i>=2.38×10<sup>-9</sup>) was novel. Of more interest, we found that <i>GALNT12</i> exhibits genetic interactions with <i>C1GALT1</i> in both galactose-deficient IgA1 levels (<i>P</i>=1.40×10<sup>-2</sup>) and disease risk (<i>P</i>=6.55×10<sup>-3</sup>). <i>GALNT12</i> mRNA expression in patients with IgA nephropathy was significantly lower compared with healthy controls.<h4>Conclusions</h4>Our data identify <i>GALNT12</i> as a novel gene associated with galactose-deficient IgA1 and suggest novel genetic interactions. These findings support a key role of genetically conferred dysregulation of galactose-deficient IgA1 in the development of IgA nephropathy.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2026-05-30T15:10:27.853Z","creation":"2025-04-19T22:38:49.513Z"},"accession":"S-EPMC7920185","cross_references":{"pubmed":["33593824"],"doi":["10.1681/ASN.2020060823","10.1681/asn.2020060823"]}}