{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:41:53Z","timestamp":1790797313999,"version":"4.1.0"},"reference-count":63,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T00:00:00Z","timestamp":1555545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"name":"The Engles Fund for TSC and LAM research"},{"name":"John Adler"},{"DOI":"10.13039\/100005963","name":"LAM Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2019,3,19]]},"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Lymphangioleiomyomatosis (LAM) occurs either associated with tuberous sclerosis complex (TSC) or as sporadic disease (S-LAM). Risk factors for development of S-LAM are unknown. We hypothesised that DNA sequence variants outside of<jats:italic>TSC2<\/jats:italic>\/<jats:italic>TSC1<\/jats:italic>might be associated with susceptibility for S-LAM and performed a genome-wide association study (GWAS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genotyped and imputed data on 5\u200a426\u200a936 single nucleotide polymorphisms (SNPs) in 426 S-LAM subjects were compared, using conditional logistic regression, with similar data from 852 females from COPDGene in a matched case\u2013control design. For replication studies, genotypes for 196 non-Hispanic White female S-LAM subjects were compared with three different sets of controls. RNA sequencing and immunohistochemistry analyses were also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two noncoding genotyped SNPs met genome-wide significance: rs4544201 and rs2006950 (p=4.2\u00d710<jats:sup>\u22128<\/jats:sup>and 6.1\u00d710<jats:sup>\u22129<\/jats:sup>, respectively), which are in the same 35\u2005kb linkage disequilibrium block on chromosome 15q26.2. This association was replicated in an independent cohort.<jats:italic>NR2F2<\/jats:italic>(nuclear receptor subfamily 2 group F member 2), a nuclear receptor and transcription factor, was the only nearby protein-coding gene.<jats:italic>NR2F2<\/jats:italic>expression was higher by RNA sequencing in one abdominal LAM tumour and four kidney angiomyolipomas, a LAM-related tumour, compared with all cancers from The Cancer Genome Atlas. Immunohistochemistry showed strong nuclear expression in both LAM and angiomyolipoma tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SNPs on chromosome 15q26.2 are associated with S-LAM, and chromatin and expression data suggest that this association may occur through effects on<jats:italic>NR2F2<\/jats:italic>expression, which potentially plays an important role in S-LAM development.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.00329-2019","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T12:15:21Z","timestamp":1555589721000},"page":"1900329","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["A genome-wide association study implicates<i>NR2F2<\/i>in lymphangioleiomyomatosis 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