A genotype-first approach to defining the subtypes of a complex disease

Holly A. Stessman; Raphael Bernier; Evan E. Eichler

doi:10.1016/j.cell.2014.02.002

A genotype-first approach to defining the subtypes of a complex disease

Holly A. Stessman, Raphael Bernier, Evan E. Eichler

Research output: Contribution to journal › Comment/debate › peer-review

130 Scopus citations

Abstract

Medical genetics typically entails the detailed characterization of a patient's phenotypes followed by genotyping to discover the responsible gene or mutation. Here, we propose that the systematic discovery of genetic variants associated with complex diseases such as autism are progressing to a point where a reverse strategy may be fruitful in assigning the pathogenic effects of many different genes and in determining whether particular genotypes manifest as clinically recognizable phenotypes. This "genotype-first" approach for complex disease necessitates the development of large, highly integrated networks of researchers, clinicians, and patient families, with the promise of improved therapies for subsets of patients.

Original language	English (US)
Pages (from-to)	872-877
Number of pages	6
Journal	Cell
Volume	156
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2014.02.002
State	Published - Feb 27 2014
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2014.02.002

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title = "A genotype-first approach to defining the subtypes of a complex disease",

abstract = "Medical genetics typically entails the detailed characterization of a patient's phenotypes followed by genotyping to discover the responsible gene or mutation. Here, we propose that the systematic discovery of genetic variants associated with complex diseases such as autism are progressing to a point where a reverse strategy may be fruitful in assigning the pathogenic effects of many different genes and in determining whether particular genotypes manifest as clinically recognizable phenotypes. This {"}genotype-first{"} approach for complex disease necessitates the development of large, highly integrated networks of researchers, clinicians, and patient families, with the promise of improved therapies for subsets of patients.",

author = "Stessman, {Holly A.} and Raphael Bernier and Eichler, {Evan E.}",

note = "Funding Information: This work was supported, in part, by U.S. National Institute of Mental Health (NIMH) grant MH101221 and by the Simons Foundation Autism Research Initiative (SFARI) 303241 to E.E.E. E.E.E. is an investigator of the Howard Hughes Medical Institute. E.E.E. is on the scientific advisory boards (SABs) of DNAnexus, Inc. and was an SAB member of Pacific Biosciences, Inc. (2009–2013) and SynapDx Corp. (2011–2013).",

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N2 - Medical genetics typically entails the detailed characterization of a patient's phenotypes followed by genotyping to discover the responsible gene or mutation. Here, we propose that the systematic discovery of genetic variants associated with complex diseases such as autism are progressing to a point where a reverse strategy may be fruitful in assigning the pathogenic effects of many different genes and in determining whether particular genotypes manifest as clinically recognizable phenotypes. This "genotype-first" approach for complex disease necessitates the development of large, highly integrated networks of researchers, clinicians, and patient families, with the promise of improved therapies for subsets of patients.

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