Impaired collagen chaperone results in preterm PROM

Abstract

It is well known that risk for many polygenic diseases, such as coronary heart disease, hypertension, prostate cancer, and asthma, varies according to race, ethnicity, or population. This phenomenon has led to the suggestion that mapping by admixture linkage disequilibrium (MALD) may hold the power to elucidate the mutations that underlie these common and complex chronic diseases (1). However, the concept of race is ill-defined because self-reported racial descriptors are often not accurate indicators of ancestry and are frequently confounded with sociocultural factors that underlie the risk of disease. Consequently, there has been significant debate concerning the scientific value of incorporating race or ethnicity descriptors into biomedical research (2–4). Indeed, a recent metaanalysis of 43 validated gene–disease associations across 697 populations found no race-associated variation in risk of disease in 86% of cases (5). However, this remarkable level of homogeneity of genotypic associations across populations does not imply that the risk of disease is homogeneous across populations. In fact, 58% of the markers demonstrated allelic heterogeneity among the control populations, which suggests that these diseases have population-specific differences in risk. Therefore, over one-half of the studied gene–disease associations should theoretically be detectable in recently admixed populations by association analysis. MALD has yet to successfully identify genetic variants responsible for polygenic disease (6) primarily because of the lack, until recently, of dense maps of validated markers with large frequency differences between populations (7). In this issue of PNAS, Wang et al. (8) report the identification of the first ancestry-informative mutation responsible for an increased risk of preterm, premature rupture of membranes (PPROM) in African Americans. PPROM …