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Review
. 2010;12(1):37-46.
doi: 10.31887/DCNS.2010.12.1/aneed.

Whole genome association studies in complex diseases: where do we stand?

Anna C Need  1 , David B Goldstein
Affiliations
Review

Whole genome association studies in complex diseases: where do we stand?

Anna C Need et al. Dialogues Clin Neurosci. 2010.

Abstract
in English, Spanish, French

Hundreds of genome-wide association studies have been performed in recent years in order to try to identify common variants that associate with complex disease. These have met with varying success. Some of the strongest effects of common variants have been found in late-onset diseases and in drug response. The major histocompatibility complex has also shown very strong association with a variety of disorders. Although there have been some notable success stories in neuropsychiatric genetics, on the whole, common variation has explained little of the high heritability of these traits. In contrast, early studies of rare copy number variants have led rapidly to a number of genes and loci that strongly associate with neuropsychiatric disorders. It is likely that the use of whole-genome sequencing to extend the study of rare variation in neuropsychiatry will greatly advance our understanding of neuropsychiatric genetics.

En los últimos años se han realizado cientos de estudios de asociación del genoma completo tratando de identificar variantes comunes que se asocien con enfermedades complejas, los que han tenido logros variables. En enfermedades de aparición tardía y en la respuesta a fármacos se han encontrado algunos de los efectos más potentes de variantes comunes. El complejo mayor de histocompatibilidad también ha mostrado una asociación muy fuerte con una variedad de trastornos. Aunque han existido algunos casos destacados de éxito en la genética neuropsiquiátrica, en conjunto, la variación común ha explicado sólo parte de la alta herencia de estos rasgos. Por otra parte, los estudios iniciales de variantes raras del número de la copia han conducido rápidamente a asociaciones potentes entre un número de genes y loci con trastornos neuropsiquiátricos. Es posible que el empleo de la secuenciación de todo el genoma se extienda al estudio de variaciones raras en neuropsiquiatría y se progrese enormemente en la comprensión de la genética neuropsiquiátrica.

Ces dernières années, des centaines d'études d'association sur le génome entier ont tenté d'identifier des variants communs associés aux maladies complexes, ceci avec un succès mitigé. Certains des effets les plus marqués des variants communs ont été retrouvés dans les maladies à début tardif et dans la réponse au médicament. Le complexe majeur d'histocompatibilité a montré également une très forte association avec différents troubles. Malgré quelques succès notables en génétique neuropsychiatrique, dans l'ensemble, la très haute héritabilité de ces caractères a été peu expliquée par les variants communs. Au contraire, les premières études de variations rares du nombre de copies ont permis rapidement d'affirmer une forte association de nombreux gènes et loci à des maladies neuropsychiatriques. Il est probable que l'utilisation du séquençage du génome entier pour améliorer l'étude des variations rares en neuropsychiatrie va permettre de faire avancer de manière significative notre compréhension de la génétique neuropsychiatrique.

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Figures

Figure 1.
Figure 1.. The power to detect a causal variant that is perfectly tagged by a genotyped marker (assuming dominant model, minor allele frequency=0.2, frequency of disease is 1% and equa numbers of cases and controls). To have a good chance of detecting a variant with a relative risk of 1.2, about 2000 cases and controls are needed
See this image and copyright information in PMC

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