Software for analyzing global family-based association studies

Orofacial clefts are a major global public health problem, and improving health outcomes for infants and their families requires understanding the complex genetic mechanisms that contribute to the formation of such congenital anomalies. In turn, increasing our understanding of such genetic mechanisms requires that genetic data represent global populations. Improving human health requires having data that represents the full kaleidoscope of human diversity as well as family structure. The present work was motivated by a dataset at the intersection of orofacial clefts as a public health problem and the need for genetic data to represent families from global populations. The Pittsburgh Orofacial Cleft studies included an international, family-based, case-control genome-wide association study (GWAS) of orofacial cleft conditions designed to analyze the genetic factors associated with clefting in global populations. Cleft patients, most of whom were children, were recruited into the study along with their parents, siblings, and extended family members. Families were recruited from data collection sites that represented fourteen countries across five continents. These genetic data have a complex correlation structure, with family groups nested inside each data collection site.