TY - JOUR
T1 - Thirty-seven candidate genes for polycystic ovary syndrome
T2 - Strongest evidence for linkage is with follistatin
AU - Urbanek, Margrit
AU - Legro, Richard S.
AU - Driscoll, Deborah A.
AU - Azziz, Ricardo
AU - Ehrmann, David A.
AU - Norman, Robert J.
AU - Strauss, Jerome F.
AU - Spielman, Richard S.
AU - Dunaif, Andrea
PY - 1999/7/20
Y1 - 1999/7/20
N2 - Polycystic 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%; χ2 = 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 (χ2 ≥ 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; χ2 = 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.
AB - Polycystic 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%; χ2 = 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 (χ2 ≥ 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; χ2 = 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.
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U2 - 10.1073/pnas.96.15.8573
DO - 10.1073/pnas.96.15.8573
M3 - Article
C2 - 10411917
AN - SCOPUS:0033587746
SN - 0027-8424
VL - 96
SP - 8573
EP - 8578
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -