A genealogical assessment of familial clustering of anorectal malformations

Abstract

Familial recurrence of anorectal malformations (ARMs) has been reported in single institution case series and in two population-based studies. Here, we investigate the familial aggregation of ARMs using well-established, unbiased methods in a population genealogy of Utah. Study subjects included 255 ARM cases identified from among the two largest healthcare providers in Utah with linked genealogy data using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. The genealogical index of familiality (GIF) statistic, which compares the average pair-wise relatedness of cases to sets of matched controls, was used to test excess familial clustering. We also estimated relative risks (RRs) for ARM and associated phenotypes in relatives of cases adjusting for age-, sex-, and birthplace. Significant excess familial clustering was observed for all ARM subjects (GIF p < 1e-3). Significant RR estimates for ARM (RR = 15.6, p = 3.3e-6), and for almost all co-morbid birth defects previously associated with ARM, were observed among first-degree relatives of ARM case subjects. This genealogically-based population survey of familial aggregation of ARMs confirms the presence of a heritable component to ARMs and provides unbiased risk estimates to relatives of cases, which may have clinical utility.

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Acknowledgements

Partial support for all data sets within the Utah Population Database (UPDB) was provided by Huntsman Cancer Institute, Huntsman Cancer Foundation, University of Utah, and the Huntsman Cancer Institute’s Cancer Center Support grant, P30 CA42014 from National Cancer Institute. Financial support for data analysis was provided by Primary Children’s Foundation, Salt Lake City, UT, USA.

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Correspondence to Michael D. Rollins.

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Teerlink, C.C., Bernhisel, R., Cannon-Albright, L.A. et al. A genealogical assessment of familial clustering of anorectal malformations. J Hum Genet 63, 1029–1034 (2018). https://doi.org/10.1038/s10038-018-0487-y

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