title: Replication of genetic loci for sarcoidosis in US black women: data from the Black Women's Health Study.
abstract: In the United States, incidence and mortality from sarcoidosis, a chronic, granulomatous disease, are increased in black women. In data from the Black Women's Health Study, a follow-up of US black women, we assessed two SNPs (rs2076530 and rs9268480) previously identified in the BTNL2 gene (chromosome 6p21), of which rs4424066 and rs3817963 are perfect proxies, to determine if they represent independent signals of disease risk. We also assessed whether local ancestry in four genomic regions previously identified through admixture mapping was associated with sarcoidosis. Finally, we assessed the relation of global percent African ancestry to risk. We conducted a nested case-control study of 486 sarcoidosis cases and 943 age- and geography-matched controls. Both BTNL2 SNPs were associated with risk of sarcoidosis in separate models, but in a combined analysis the increased risk was due to the A-allele of the rs3817963 SNP; each copy of the A-allele was associated with a 40 % increase in risk of sarcoidosis (p = 0.02) and was confirmed by our haplotypic analysis. Local African ancestry around the rs30533 ancestry informative marker at chromosome 5q31 was associated with a 29 % risk reduction (p = 0.01). Therefore, we adjusted our analysis of global African ancestry for number of copies of African alleles in rs30533. Subjects in the highest quintile of percent African ancestry had a 54 % increased risk of sarcoidosis. The present results from a population of African-American women support the role of the BTNL2 gene and the 5q31 locus in the etiology of sarcoidosis, and also demonstrate that percent African ancestry is associated with disease risk.
authors.affiliation: Slone Epidemiology Center, Boston University, Boston, USA. yvettec@bu.edu
authors.forename: Yvette
authors.initials: Y
authors.lastname: Cozier
authors.forename: Edward
authors.initials: E
authors.lastname: Ruiz-Narvaez
authors.forename: Craig
authors.initials: C
authors.lastname: McKinnon
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Berman
authors.forename: Lynn
authors.initials: L
authors.lastname: Rosenberg
authors.forename: Julie
authors.initials: J
authors.lastname: Palmer
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000483:Alleles; D000071797:Butyrophilins; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012507:Sarcoidosis / Q000453:epidemiology / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: C408263:BTNL2 protein, human; D000071797:Butyrophilins; D008562:Membrane Glycoproteins
references.citation: Tissue Antigens. 2009 Oct;74(4):322-9
references.pmid: 19659809
references.citation: Ann Hum Genet. 2000 Mar;64(Pt 2):171-86
references.pmid: 11246470
references.citation: Genes Immun. 2006 Jul;7(5):359-65
references.pmid: 16724073
references.citation: Sarcoidosis Vasc Diffuse Lung Dis. 2005 Jun;22(2):115-22
references.pmid: 16053026
references.citation: Nat Genet. 2005 Oct;37(10):1113-8
references.pmid: 16186815
references.citation: J Clin Epidemiol. 2010 Nov;63(11):1179-94
references.pmid: 20685078
references.citation: Chest. 2011 Jan;139(1):144-50
references.pmid: 20595459
references.citation: PLoS One. 2012;7(8):e43907
references.pmid: 22952805
references.citation: J R Coll Physicians Lond. 1985 Jul;19(3):179-83
references.pmid: 4045768
references.citation: Br J Dis Chest. 1985 Jan;79(1):27-36
references.pmid: 3986110
references.citation: Nature. 2003 Dec 18;426(6968):789-96
references.pmid: 14685227
references.citation: Genes Immun. 2011 Mar;12(2):67-77
references.pmid: 21179114
references.citation: Semin Respir Infect. 1998 Sep;13(3):166-73
references.pmid: 9764947
references.citation: Genomics. 2001 Feb 1;71(3):351-62
references.pmid: 11170752
references.citation: Am J Epidemiol. 2001 Jan 15;153(2):188-93
references.pmid: 11159165
references.citation: Arthritis Rheum. 2005 Nov;52(11):3596-602
references.pmid: 16255050
references.citation: Nat Genet. 2005 Apr;37(4):357-64
references.pmid: 15735647
references.citation: East Afr Med J. 1987 Jul;64(7):504-7
references.pmid: 3691366
references.citation: Respir Res. 2005 Dec 10;6:145
references.pmid: 16336695
references.citation: Hum Immunol. 2011 Apr;72(4):342-7
references.pmid: 21256912
references.citation: Nature. 1992 Apr 16;356(6370):607-9
references.pmid: 1313950
references.citation: Am J Respir Crit Care Med. 2011 Jun 1;183(11):1524-30
references.pmid: 21330454
references.citation: Sarcoidosis Vasc Diffuse Lung Dis. 2009 Jul;26(2):162-6
references.pmid: 20560297
references.citation: Am J Respir Crit Care Med. 2001 Dec 1;164(11):2085-91
references.pmid: 11739139
references.citation: Epidemiol Rev. 1983;5:124-56
references.pmid: 6357818
references.citation: Nat Genet. 2008 Jun;40(6):710-2
references.pmid: 18438406
references.citation: Trans R Soc Trop Med Hyg. 1987;81(6):1027-9
references.pmid: 3503404
references.citation: Hum Hered. 2002;53(2):79-91
references.pmid: 12037407
references.citation: Am J Respir Crit Care Med. 2001 Sep 1;164(5):840-6
references.pmid: 11549543
references.citation: J Clin Epidemiol. 1999 Dec;52(12):1173-86
references.pmid: 10580780
references.citation: J Immunol. 2006 Jun 15;176(12):7354-60
references.pmid: 16751379
references.citation: Am J Hum Genet. 2003 Jun;72(6):1492-1504
references.pmid: 12817591
references.citation: N Engl J Med. 2009 Nov 19;361(21):2066-78
references.pmid: 19923578
references.citation: Am Rev Respir Dis. 1961 Nov;84(5)Pt 2:162
references.pmid: 13924598
references.citation: Am J Respir Crit Care Med. 2003 Feb 1;167(3):444-9
references.pmid: 12554629
references.citation: Am J Epidemiol. 2011 Mar 1;173(5):587-92
references.pmid: 21262910
references.citation: Tissue Antigens. 2007 Sep;70(3):219-27
references.pmid: 17661910
references.citation: Am J Respir Crit Care Med. 2003 May 1;167(9):1225-31
references.pmid: 12615619
references.citation: Clin Respir J. 2011 Apr;5(2):105-11
references.pmid: 21410903
references.citation: Am J Hum Genet. 2005 Sep;77(3):491-9
references.pmid: 16080124
references.citation: S Afr Med J. 1977 Oct 1;52(15):602-6
references.pmid: 918803
references.citation: Hum Hered. 2003;55(4):179-90
references.pmid: 14566096
references.citation: Trop Geogr Med. 1984 Sep;36(3):231-6
references.pmid: 6506201
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: N Engl J Med. 2007 Nov 22;357(21):2153-65
references.pmid: 18032765
references.citation: Genes Immun. 2005 Sep;6(6):509-18
references.pmid: 15951742
references.citation: Clin Chest Med. 1997 Dec;18(4):681-94
references.pmid: 9413652
references.citation: Ann Epidemiol. 2004 Feb;14(2):117-22
references.pmid: 15018884