title: Genetic ancestry affects the phenotype of normogonadotropic anovulatory (WHOII) subfertility.
abstract: BACKGROUND
  Normogonadotropic (World Health Organization category II) anovulation is the most frequent cause of reduced fertility. Anovulation is associated with endocrine changes, i.e. hyperandrogenism, obesity, and insulin resistance. However, the phenotype is notoriously heterogeneous, depending on population characteristics and diagnostic criteria.
  
  
  OBJECTIVE
  Our objective was to study the phenotype of normogonadotropic anovulatory women among various ethnic subgroups that coexist in an urban community (The Netherlands). Moreover, we studied whether genetic ancestry testing can be used to identify bio-geographic ancestry and predict the phenotype of individual patients.
  
  
  METHODS
  A standardized clinical and endocrine examination was performed in 1517 normogonadotropic anovulatory women. Bio-geographic ancestry was ascertained by questionnaire and genetic testing (637 cases), using a set of 10 previously validated ancestry informative markers.
  
  
  RESULTS
  Subgroups constituted individuals from northwestern European (n = 774), Mediterranean European (north of Sahara and Middle East, n = 220), African (n = 111), Southeast Asian (n = 53), and Hindustani (n = 83) origin. Phenotypic differences included fasting insulin levels, androgen levels, and the frequency of hyperandrogenism (ranging from 76% in Mediterranean-European women to 41% in northwestern European women). Genetic ancestry testing was able to identify population structure on a continental level, i.e. European, African and Southeast Asian descent. We did not observe improved informativeness when genotype data were added to the prediction model.
  
  
  CONCLUSIONS
  Population differences add to the phenotype of normogonadotropic anovulation and need to be taken into account when evaluating the individual patient. Although effective on a continental level, the present set of ancestry markers was not sufficiently effective to describe all ethnic variation in the phenotype of anovulatory subfertility.
authors.affiliation: Division of Reproductive Medicine, Department of Gynecology and Obstetrics, Erasmus MC University Medical Center, 3000 CA Rotterdam, The Netherlands. o.valkenburg@erasmusmc.nl
authors.forename: O
authors.initials: O
authors.lastname: Valkenburg
authors.forename: O
authors.initials: O
authors.lastname: Lao
authors.forename: I
authors.initials: I
authors.lastname: Schipper
authors.forename: Y
authors.initials: Y
authors.lastname: Louwers
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: M
authors.initials: M
authors.lastname: Kayser
authors.forename: J S E
authors.initials: JS
authors.lastname: Laven
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000235:genetics*; D007247:Infertility, Female / Q000097:blood / Q000235:genetics*; D007328:Insulin / Q000097:blood; D008297:Male; D010641:Phenotype; D044465:White People / Q000235:genetics
chemical_list: D000728:Androgens; D007328:Insulin