Primary ovarian insufficiency has strong familiality: results of a multigenerational genealogical study

Objective

To determine the familiality of primary ovarian insufficiency (POI) at population level through examination of multigenerational genealogical information linked to electronic medical records.

Design

Case-control study.

Setting

Not applicable.

Patient(s)

Women with POI were identified using International Classification of Disease 9 and 10 codes in electronic medical records (1995–2021) from 2 major health care systems in Utah and reviewed for accuracy. Cases were linked to genealogy information in the Utah Population Database (UPDB). All included POI cases (n = 396) were required to have genealogy information available for at least 3 generations of ancestors. The risk of POI in relatives was compared with population rates for POI matched by age, sex, and birthplace.

Intervention(s)

Not applicable.

Main Outcome Measure(s)

Relative risk of POI in first-, second-, and third-degree relatives.

Result(s)

We identified 396 validated cases of POI with an associated 2,132 first-degree relatives, 5,245 second-degree relatives, and 10,853 third-degree relatives. We found an increased risk of POI among the extended relatives of cases. Specifically, first-degree relatives demonstrated an 18-fold increased risk of POI compared with controls relative risk ([RR],18.52 95% confidence interval [CI], 10.12–31.07), second-degree relatives demonstrated a 4-fold increase (RR, 4.21; CI, 1.15–10.79), and third-degree relatives demonstrated a 2.7-fold increase (RR, 2.65; CI, 1.14–5.21]).

Conclusion(s)

This is the first population-based study to assess the familial clustering of POI. The data demonstrate excess familiality, familial clustering of POI in excess compared with matched population rates of disease, among first-, second-, and third-degree relatives. These findings support a genetic contribution to POI.