Heritability of subfertility among Danish twins

Linda Juel Ahrenfeldt; Sören Möller; Maarten Wensink; Tina Kold Jensen; Kaare Christensen; Rune Lindahl-Jacobsen

doi:10.1016/j.fertnstert.2020.03.014

Heritability of subfertility among Danish twins

Fertil Steril. 2020 Sep;114(3):618-627. doi: 10.1016/j.fertnstert.2020.03.014. Epub 2020 Jul 2.

Authors

Linda Juel Ahrenfeldt¹, Sören Möller², Maarten Wensink³, Tina Kold Jensen⁴, Kaare Christensen⁵, Rune Lindahl-Jacobsen³

Affiliations

¹ Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark; The Danish Twin Registry, Department of Public Health, University of Southern Denmark, Odense, Denmark. Electronic address: lahrenfeldt@health.sdu.dk.
² OPEN - Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
³ Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark; Interdisciplinary Centre on Population Dynamics (CPop), University of Southern Denmark, Odense, Denmark.
⁴ Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.
⁵ Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark; The Danish Twin Registry, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.

PMID: 32624213
DOI: 10.1016/j.fertnstert.2020.03.014

Abstract

Objective: To investigate the relative contribution of genetic and environmental components to subfertility.

Design: Twin design using a quantitative genetic liability threshold model that splits the variation of subfertility into additive genetic effects, common environmental effects, and unique environmental effects.

Setting: Not applicable.

Patients: A total of 9053 Danish monozygotic and dizygotic same-sex twins aged 18+ years from nationwide twin surveys (twins born 1931-1976).

Intervention: Not applicable.

Main outcome measures: Time to pregnancy (TTP) restricted to first pregnancy as a binary outcome, with a cut-off point of 10 months.

Results: Based on the Akaike information criterion, a model including additive genetic and unique environmental factors resulted in the best model fit. For females, the relative contribution of additive genetic factors to TTP was 28% (95% confidence interval [CI] 15%, 41%), whereas unique environmental factors explained 72% (95% CI 59%, 85%). For males, additive genetic factors explained 4% (95% CI 0%, 22%) of the variation in TTP, while unique environmental factors accounted for 96% (95% CI 78%, 100%). Results were overall similar for the crude model and consistent across surveys.

Conclusion: Unique environmental factors explain most of the observed variation in subfertility, when measured as waiting time to pregnancy.

Keywords: Time to pregnancy fecundity; heritability; subfertility; twins.

Publication types

Twin Study

MeSH terms

Aged
Cross-Sectional Studies
Denmark
Environment
Female
Fertility / genetics*
Genetic Predisposition to Disease
Heredity
Humans
Infertility, Female / diagnosis
Infertility, Female / genetics*
Infertility, Female / physiopathology
Infertility, Male / diagnosis
Infertility, Male / genetics*
Infertility, Male / physiopathology
Male
Middle Aged
Phenotype
Risk Assessment
Risk Factors
Sex Factors
Time-to-Pregnancy / genetics
Twins, Dizygotic / genetics*
Twins, Monozygotic / genetics*