PMID- 10411917
OWN - NLM
STAT- MEDLINE
DCOM- 19990823
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 15
DP  - 1999 Jul 20
TI  - Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence
      for linkage is with follistatin.
PG  - 8573-8
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%; 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.
FAU - Urbanek, M
AU  - Urbanek M
AD  - Departments of Genetics, University of Pennsylvania School of Medicine,
      Philadelphia, PA 19104, USA.
FAU - Legro, R S
AU  - Legro RS
FAU - Driscoll, D A
AU  - Driscoll DA
FAU - Azziz, R
AU  - Azziz R
FAU - Ehrmann, D A
AU  - Ehrmann DA
FAU - Norman, R J
AU  - Norman RJ
FAU - Strauss, J F 3rd
AU  - Strauss JF 3rd
FAU - Spielman, R S
AU  - Spielman RS
FAU - Dunaif, A
AU  - Dunaif A
LA  - eng
GR  - K08HD0118/HD/NICHD NIH HHS/United States
GR  - M01 RR010732/RR/NCRR NIH HHS/United States
GR  - U54 HD034449/HD/NICHD NIH HHS/United States
GR  - M01 RR002635/RR/NCRR NIH HHS/United States
GR  - R01DK40605/DK/NIDDK NIH HHS/United States
GR  - R01 DK040605/DK/NIDDK NIH HHS/United States
GR  - T32 DK007314/DK/NIDDK NIH HHS/United States
GR  - U54 HD34449/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Follistatin)
RN  - 0 (Genetic Markers)
RN  - 0 (Glycoproteins)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
CIN - Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8315-7. PMID: 10411866
MH  - Chromosome Mapping
MH  - Cytochrome P-450 Enzyme System/genetics
MH  - Female
MH  - Follistatin
MH  - *Genetic Linkage
MH  - Genetic Markers
MH  - Genotype
MH  - Glycoproteins/*genetics
MH  - Humans
MH  - Hyperandrogenism/genetics
MH  - Nuclear Family
MH  - Oligomenorrhea/genetics
MH  - Phenotype
MH  - Polycystic Ovary Syndrome/*genetics
PMC - PMC17558
EDAT- 1999/07/21 10:00
MHDA- 2001/03/28 10:01
CRDT- 1999/07/21 10:00
PHST- 1999/07/21 10:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/07/21 10:00 [entrez]
AID - 10.1073/pnas.96.15.8573 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8573-8. doi:
      10.1073/pnas.96.15.8573.