Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
16080113
TITLE
Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26.
ABSTRACT
Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometrium in sites outside the uterus. Its cause remains uncertain despite >50 years of hypothesis-driven research, and thus the therapeutic options are limited. Disease predisposition is inherited as a complex genetic trait, which provides an alternative route to understanding the disease. We seek to identify susceptibility loci, using a positional-cloning approach that starts with linkage analysis to identify genomic regions likely to harbor these genes. We conducted a linkage study of 1,176 families (931 from an Australian group and 245 from a U.K. group), each with at least two members--mainly affected sister pairs--with surgically diagnosed disease. We have identified a region of significant linkage on chromosome 10q26 (maximum LOD score [MLS] of 3.09; genomewide P = .047) and another region of suggestive linkage on chromosome 20p13 (MLS = 2.09). Minor peaks (with MLS > 1.0) were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and 17. This is the first report of linkage to a major locus for endometriosis. The findings will facilitate discovery of novel positional genetic variants that influence the risk of developing this debilitating disease. Greater understanding of the aberrant cellular and molecular mechanisms involved in the etiology and pathophysiology of endometriosis should lead to better diagnostic methods and targeted treatments.
DATE PUBLISHED
2005 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2005/03/09
accepted 2005/06/21
aheadofprint 2005/07/21
pubmed 2005/08/05 09:00
medline 2006/02/07 09:00
entrez 2005/08/05 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Treloar SA Treloar Susan A SA Cooperative Research Centre for Discovery of Genes for Common Human Diseases, Melbourne, Australia. Sue.Treloar@qimr.edu.au
Wicks J Wicks Jacqueline J
Nyholt DR Nyholt Dale R DR
Montgomery GW Montgomery Grant W GW
Bahlo M Bahlo Melanie M
Smith V Smith Vicki V
Dawson G Dawson Gary G
Mackay IJ Mackay Ian J IJ
Weeks DE Weeks Daniel E DE
Bennett ST Bennett Simon T ST
Carey A Carey Alisoun A
Ewen-White KR Ewen-White Kelly R KR
Duffy DL Duffy David L DL
O'connor DT O'connor Daniel T DT
Barlow DH Barlow David H DH
Martin NG Martin Nicholas G NG
Kennedy SH Kennedy Stephen H SH
INVESTIGATORS
JOURNAL
VOLUME: 77
ISSUE: 3
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2005
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Eur J Hum Genet. 2001 Nov;9(11):855-9 11781703
Cites Nat Genet. 2002 Jan;30(1):97-101 11731797
Cites Ann N Y Acad Sci. 2002 Mar;955:239-51; discussion 293-5, 396-406 11949952
Cites Fertil Steril. 2002 Oct;78(4):679-85 12372440
Cites Semin Reprod Med. 2003 May;21(2):111-8 12917780
Cites Genet Epidemiol. 2004 Feb;26(2):88-96 14748008
Cites Hum Reprod. 2004 Feb;19(2):448-55 14747196
Cites Am J Hum Genet. 2004 Mar;74(3):403-17 14750073
Cites Am J Hum Genet. 2004 Mar;74(3):432-43 14752704
Cites Am J Hum Genet. 2004 Mar;74(3):482-94 14968411
Cites Reproduction. 2004 Mar;127(3):293-304 15016949
Cites J Clin Endocrinol Metab. 2004 May;89(5):2390-6 15126568
Cites Am J Hum Genet. 2004 Jun;74(6):1294-302 15124101
Cites Twin Res. 2004 Apr;7(2):211-6 15169605
Cites Clin Genet. 1979 Feb;15(2):126-36 367641
Cites Fertil Steril. 1985 Mar;43(3):351-2 3979573
Cites Nucleic Acids Res. 1988 Feb 11;16(3):1215 3344216
Cites Am J Hum Genet. 1990 Feb;46(2):229-41 2301393
Cites Am J Hum Genet. 1993 Feb;52(2):362-74 8430697
Cites Cancer Res. 1995 May 1;55(9):1922-6 7728760
Cites J Assist Reprod Genet. 1995 Jan;12(1):32-4 7580007
Cites Am J Hum Genet. 1996 Jun;58(6):1347-63 8651312
Cites Am J Hum Genet. 1997 Jan;60(1):217-27 8981965
Cites Obstet Gynecol Clin North Am. 1997 Jun;24(2):235-58 9163765
Cites Fertil Steril. 1997 Oct;68(4):585-96 9341595
Cites Am J Hum Genet. 1997 Dec;61(6):1431-44 9399893
Cites Am J Hum Genet. 1998 Apr;62(4):994-7 9529350
Cites Am J Hum Genet. 1998 Jul;63(1):259-66 9634505
Cites Am J Hum Genet. 1998 Sep;63(3):870-9 9718328
Cites Genomics. 1998 Aug 15;52(1):9-16 9740666
Cites Hum Reprod Update. 1998 Sep-Oct;4(5):736-40 10027628
Cites Fertil Steril. 1999 Apr;71(4):701-10 10202882
Cites Lancet. 2004 Nov 13-19;364(9447):1789-99 15541453
Cites Hum Reprod Update. 2000 Jan-Feb;6(1):37-44 10711828
Cites Genetics. 2000 Jul;155(3):1369-78 10880495
Cites Am J Hum Genet. 2000 Aug;67(2):282-8 10884360
Cites Am J Hum Genet. 2000 Sep;67(3):727-36 10924406
Cites Cancer Res. 2000 Dec 15;60(24):7052-6 11156411
Cites Hum Hered. 2001;51(4):217-25 11287743
Cites Eur J Obstet Gynecol Reprod Biol. 2001 May;96(1):21-34 11311757
Cites Curr Opin Obstet Gynecol. 2001 Jun;13(3):309-14 11396656
Cites Bioinformatics. 2001 Aug;17(8):742-3 11524377
Cites Mol Hum Reprod. 2001 Nov;7(11):1073-8 11675474
Cites Am J Hum Genet. 2001 Dec;69(6):1357-69 11593451
Cites Fertil Steril. 2001 Nov;76(5):1019-22 11704127
Cites Hum Reprod. 2002 Mar;17(3):555-9 11870102
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Australia epidemiology
Chromosome Mapping epidemiology
Chromosomes, Human, Pair 10 genetics
Endometriosis genetics
Female genetics
Genetic Linkage genetics
Genetic Predisposition to Disease genetics
Genome, Human genetics
Great Britain epidemiology
Humans epidemiology
Lod Score epidemiology
Multifactorial Inheritance genetics
Siblings genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC1226203 NLM