The Future of Genetic Studies of Complex Human Diseases

Abstract

The identification of the genetic basis of complex human diseases such as schizophrenia and diabetes has proven difficult. In their Perspective, Risch and Merikangas propose that we can best accomplish this goal by combining the power of the human genome project with association studies, a method for determining the basis of a genetic disease.

Genome‐wide association studies of multiple sclerosis

“…The development of genetic maps covering much of the genome led to linkage analyses in extended MS affected families from a number of countries, primarily of European ancestry 23, 24, 25, 26, 27, 28, 29, 30, 31, 32. These validated the HLA association but showed no significant linkage to loci outside the MHC.…”

“…This technological development enabled the profiling of thousands of samples in a single study and prompted a shift away from family studies, where samples are necessarily limited and ascertainment challenging, to population‐based association studies comparing unrelated cases and controls 27. These genome‐wide association studies (GWAS) compare allele frequency at each variant position of the genome between cases and controls, with significant differences implying an association to disease.…”

Autism genetics: searching for specificity and convergence

“…Given that ASD is highly prevalent, it was initially thought (consistent with the prevailing common variant-common disease model [53]) that common genetic single nucleotide polymorphism (SNP) variants (those occurring in at least 5% [54] of the population) would lead to this common disorder.…”

Intercellular adhesion molecule-1: a protective haplotype against multiple sclerosis

“…For such a sample size, the probability to detect a locus with a genotype relative risk of 2 (assuming a multiplicative model) for a nominal type I error of 5% is greater than 80%. 26 When for a marker, the uncorrected P-value was below 5% in batch 1, the remaining 289 case-parent families (batch 2) were tested.…”