Inbreeding and prereproductive mortality in the Old Order Amish. II. Genealogic epidemiology of prereproductive mortality.

The effects of offspring and parental inbreeding on prereproductive mortality (death before age 20 years) in the historical population of the Lancaster County, Pennsylvania, Old Order Amish were investigated using the Amish genealogic registry, which contains information on 42,465 births dating to the time of the pioneer migrants in the 1700s. Inbreeding coefficients for offspring and parents were computed using the path method of tracing common ancestors in the multigenerational pedigrees. In this population, prereproductive mortality declined from about 15% in the late 1800s to about 5% after 1930. Offspring inbreeding was found to be an independent predictor of prereproductive mortality after multivariate adjustment for demographic risk factors for mortality. Moreover, the higher the coefficient, the higher the relative risk of prereproductive death, and the higher the risk of multiple deaths in the same sibship. There was no evidence of declining inbreeding effects over 10 generations of continuous inbreeding, nor of any significant parental inbreeding effects. Because of the high levels of inbreeding, it could be shown that inbreeding accounts for about 40% of all prereproductive deaths in the present population. Genetic load analysis showed an average of about 1.7 lethal equivalents and a mostly mutational load.