This renewal application requests support to continue a long-term study of the genetics of hypertension in populations of West African origin. Defining the genetic architecture of hypertension remains a central challenge for cardiovascular (CV) epidemiology. To date, however, no widely replicated loci have been identified for hypertension. The genome-wide association design has proven to be effective for other complex traits. We propose to build on our population samples in West Africa, the Caribbean and the US and to create a large collaborative network that will allow a comprehensive search for genetic underpinnings of this disorder. A multi-stage design will allow discovery and replication in West African populations, and further replication in Western Hemisphere groups in contrasting environments. We will use the Affymetrix 6.0 array to conduct a genome-wide association study of blood pressure/hypertension in 2,000 Nigerians of Yoruban ethnicity to identify markers/regions of interest (data on 1,250 samples are being collected in the current grant;support is requested for 750 additional samples). Informative markers will then be typed in replication populations from West Africa (N = 4,000), as well as Brazil and the Caribbean (N = 7,500). A sub-set of the replication samples will be used to assess gene-environment interactions by comparing low vs. high risk factor status for BMI and salt intake. We will then examine consistency of the findings in large US studies of African Americans with similar data. The data will be made available for public access. Our study will also benefit from the extensive genetic data already available on the Yoruba population through the HapMap project. This project builds on many years of experience studying hypertension in Afro- origin populations. These populations have a highly informative genetic structure and genetic effects are likely to be strongest in West Africa where risk factor exposure is low. DNA samples and extensive phenotype information have already been collected on the 18,000 study participants. The design makes it possible to conduct the initial search in a population with high levels of internal genetic diversity without recent admixture and a wide range of measured BP. Access to a broad range of replication samples further makes it possible to determine the generalizability of these findings and potential gene- environment effects.
This project will conduct a genome-wide association for hypertension in the Yoruba population of Nigeria. Positive associations will be examined in a large replication sample from West Africa, and from population samples from Brazil, the Caribbean and the US. These data should help establish the genetic factors that underlie risk of hypertension and thereby contribute to an improved understanding of this important public health problem.
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