Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin

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dc.contributor.authorUrbanek, M.
dc.contributor.authorLegro, R.
dc.contributor.authorDriscoll, D.
dc.contributor.authorAzziz, R.
dc.contributor.authorEhrmann, D.
dc.contributor.authorNorman, R.
dc.contributor.authorStrauss, J.
dc.contributor.authorSpielman, R.
dc.contributor.authorDunaif, A.
dc.date.issued1999
dc.description.abstractPolycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; chi(2) = 12.97; nominal P = 3.2 x 10(-4)). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P(c) = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (chi(2) >/= 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; chi(2) = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.
dc.description.statementofresponsibilityUrbanek, Margrit ; Legro, Richard S. ; Driscoll, Deborah A. ; Azziz, Ricardo ; Ehrmann, David A. ; Norman, Robert J. ; Strauss,, Jerome F. ; Spielman, Richard S. ; Dunaif, Andrea
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 1999; 96(15):8573-8578
dc.identifier.doi10.1073/pnas.96.15.8573
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.orcidNorman, R. [0000-0002-3118-3896]
dc.identifier.urihttp://hdl.handle.net/2440/8460
dc.language.isoen
dc.publisherNATL ACAD SCIENCES
dc.source.urihttps://doi.org/10.1073/pnas.96.15.8573
dc.subjectHumans
dc.subjectPolycystic Ovary Syndrome
dc.subjectHyperandrogenism
dc.subjectOligomenorrhea
dc.subjectCytochrome P-450 Enzyme System
dc.subjectGlycoproteins
dc.subjectFollistatin
dc.subjectGenetic Markers
dc.subjectChromosome Mapping
dc.subjectNuclear Family
dc.subjectGenotype
dc.subjectPhenotype
dc.subjectFemale
dc.subjectGenetic Linkage
dc.titleThirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin
dc.typeJournal article
pubs.publication-statusPublished

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