Genome-wide association studies in kidney diseases: Quo Vadis?

Abstract

A genome-wide association (GWA) study is a genetic epidemiology approach designed to scan genetic variation across the entire human genome in order to identify genetic associations with phenotypic traits as well as the presence or absence of a disease. Hundreds of thousands of single-nucleotide polymorphisms (SNPs), the most common form of genetic variant, serve as markers. SNPs are assayed and related to diseases or health-related conditions applying bioinformatics algorithms. This has become feasible thanks to the recent technological improvements in the so-called high-throughput technologies. The analysis identifies regions (loci) with statistically significant differences in allele or genotype frequencies between cases and controls and so the variations are said to be ‘associated’ with the disease. The completion of the Human Genome Project in 2003 and then the HapMap Project allowed GWA studies to be conducted, cataloguing common human genetic variants and providing the ‘tag SNPs’ (markers) included in the DNA microarrays used for the genotyping [1]. GWA studies are usually structured in four parts (1) collection of a large number of blood sample from individuals with the disease/trait of interest and from a control group; (2) DNA isolation and genotyping; (3) statistical tests for associations between the SNPs and the disease/trait; (4) replication of identified associations in an independent population sample and examination of functional implications experimentally [2]. Four hundred replicated associations have now been reported for more than 70 common diseases, conditions and biological parameters (see the National Human Genome Research Institute catalogue of published GWA studies, http://www.genome.gov/gwastudies) [3]. In this review, we present the results of GWA studies performed for kidney diseases published to date (Table 1) and point out the main features of this intricate methodological approach in order to better understand what opportunities are offered in nephrology. Studies have been identified through ‘HuGE Navigator’, ‘A Catalog of Published Genome-Wide Association Studies’ and ‘PubMed’ search [3,4]. GWA studies in kidney diseases