Relationship between polycystic ovary syndrome and ancestry in European Americans.
OBJECTIVE
To determine whether European Americans with polycystic ovary syndrome (PCOS) exhibit genetic differences associated with PCOS status and phenotypic features.


METHODS
Case-control association study in European Americans.


METHODS
Academic center.


METHODS
Women with PCOS diagnosed with the use of the National Institutes of Health criteria (n = 532) and control women with regular menstrual cycles and no evidence of hyperandrogenism (n = 432).


METHODS
Blood was drawn for measurement of sex steroids, metabolic parameters, and genotyping.


METHODS
Associations among PCOS status, phenotype, and genetic background identified with the use of principal component analysis.


RESULTS
Principal component analysis identified five principal components (PCs). PC1 captured northwest-to-southeast European genetic variation and was associated with PCOS status. Acanthosis was associated with southern European ancestry, and larger waist:hip ratio was associated with northern European ancestry. PC2 was associated with east-to-west European genetic variation and cholesterol levels.


CONCLUSIONS
These data provide evidence for genetic influence based on European ethnicity in women with PCOS. There is also evidence for a genetic component in the phenotypic features of PCOS within a mixed European population. The data point to the need to control for population stratification in genetic studies in women of mixed European ethnicity. They also emphasize the need for better studies of PCOS prevalence and phenotype as a function of genetic background.
Department of Anesthesia, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts.
Andrew C
AC
Bjonnes
Department of Anesthesia, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts.
Richa
R
Saxena
Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, Utah. Electronic address: cwelt@genetics.utah.edu.
Corrine K
CK
Welt
D000052:Acanthosis Nigricans / Q000208:ethnology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008875:Middle Aged; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D025341:Principal Component Analysis; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D065927:Waist-Height Ratio; D044465:White People / Q000235:genetics*; D055815:Young Adult
D015415:Biomarkers; D002784:Cholesterol
European; genetics; population stratification; waist:hip ratio
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