Parent-of-origin effects on glucose homeostasis in polycystic ovary syndrome

Kristen Kobaly, Priyathama Vellanki, Ryan K. Sisk, Loren Armstrong, Ji Young Lee, Jungwha Lee, M. Geoffrey Hayes, Margrit Urbanek, Richard S. Legro, Andrea Dunaif

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Context: Polycystic ovary syndrome (PCOS) is a highly heritable complex trait. Parents of affected women have reproductive and metabolic phenotypes. Objective: We tested the hypothesis that there are parental effects on the heritability of fasting dysglycemia in women with PCOS. Design and Setting: This was a cross-sectional study at an academic medical center. Participants: Participants included 367 women with PCOS and their parents (1101 total subjects). Main Outcome Measures: We compared maternal and paternal contributions to heritability of fasting dysglycemia and to transmission of the PCOS susceptibility allele of D19S884 within the fibrillin-3 gene (D19S884-A8) on fasting dysglycemia. Results: Fathers had higher fasting glucose levels, prevalence of fasting dysglycemia and proinsulin to insulin molar ratios (P<.0001), a marker of defective insulin processing,comparedwith mothers. Heritability of fasting dysglycemia was significant in PCOS families (h 2=37%, SE=10%, P=.001). Maternal heritability (h2 = 51%, SE = 15%, P = .0009) was higher than paternal heritability (h2 = 23 %, SE = 23%, P = .186) of fasting dysglycemia after adjustment for age and body mass index. Within dysglycemic probands, there was increased maternal compared with paternal transmission of D19S884-A8 (maternal 84% vs paternal 45%, χ 2 = 6.51, P = .011). Conclusions: There was a sex difference in the parental metabolic phenotype with fathers having an increased risk of fasting dysglycemia and evidence for pancreatic β-cell dysfunction compared with mothers. However, only maternal heritability had significant effects on the prevalence of fasting dysglycemia in women with PCOS. Furthermore, there were maternal parent-of-origin effects on transmission of D19S884-A8 probands with fasting dysglycemia. These findings suggest that maternal factors, genetic and perhaps epigenetic, contribute to the metabolic phenotype in affected women.

Original languageEnglish (US)
Pages (from-to)2961-2966
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number8
DOIs
StatePublished - Aug 2014

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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