Just one year later, in a paper that had a very strong influence in the field of complex disease genetics, Rish and Merikangas (15) showed that, if complex disorders were due to common genetic variants with small effects, linkage studies would need to examine many thousands of families to identify such loci. They also showed that performing genetic association studies rather than linkage was far more powerful for discovering these loci. At that time the genotyping technologies did not allow a genome-wide scan for association and such studies were only performed in small scale for individual candidate genes and were often reserved for following up linkage signals. Today, through the use of microarrays and other similar array-based technologies, genotyping a million SNPs across the genome has become both fast and affordable and genome-wide association studies (GWAS) have mostly replaced linkage in the exploration of complex disorders. The few linkage studies that are now performed use SNP markers, genotyped in large numbers to match and exceed the high information content of microsatellites. The genetic effect sizes of common alleles uncovered by
