Rediscovering the value of families for psychiatric genetics research

David C. Glahn, V.L. Nimgaonkar, H. Raventos, Nina McCarthy, Assen Jablensky, Joanne E. Curran, L Almasy, John Blangero

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

As it is likely that both common and rare genetic variation are important for complex disease risk, studies that examine the full range of the allelic frequency distribution should be utilized to dissect the genetic influences on mental illness. The rate limiting factor for inferring an association between a variant and a phenotype is inevitably the total number of copies of the minor allele captured in the studied sample. For rare variation, with minor allele frequencies of 0.5% or less, very large samples of unrelated individuals are necessary to unambiguously associate a locus with an illness. Unfortunately, such large samples are often cost prohibitive. However, by using alternative analytic strategies and studying related individuals, particularly those from large multiplex families, it is possible to reduce the required sample size while maintaining statistical power. We contend that using whole genome sequence (WGS) in extended pedigrees provides a cost-effective strategy for psychiatric gene mapping that complements common variant approaches and WGS in unrelated individuals. This was our impetus for forming the "Pedigree-Based Whole Genome Sequencing of Affective and Psychotic Disorders" consortium. In this review, we provide a rationale for the use of WGS with pedigrees in modern psychiatric genetics research. We begin with a focused review of the current literature, followed by a short history of family-based research in psychiatry. Next, we describe several advantages of pedigrees for WGS research, including power estimates, methods for studying the environment, and endophenotypes. We conclude with a brief description of our consortium and its goals.
Original languageEnglish
Pages (from-to)523-535
JournalMolecular Psychiatry
Volume24
Issue number4
DOIs
Publication statusPublished - Apr 2019

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Genetic Research
Psychiatry
Pedigree
Genome
Psychotic Affective Disorders
Endophenotypes
Costs and Cost Analysis
Chromosome Mapping
Gene Frequency
Sample Size
Alleles
Phenotype
Research

Cite this

Glahn, D. C., Nimgaonkar, V. L., Raventos, H., McCarthy, N., Jablensky, A., Curran, J. E., ... Blangero, J. (2019). Rediscovering the value of families for psychiatric genetics research. Molecular Psychiatry, 24(4), 523-535. https://doi.org/10.1038/s41380-018-0073-x
Glahn, David C. ; Nimgaonkar, V.L. ; Raventos, H. ; McCarthy, Nina ; Jablensky, Assen ; Curran, Joanne E. ; Almasy, L ; Blangero, John. / Rediscovering the value of families for psychiatric genetics research. In: Molecular Psychiatry. 2019 ; Vol. 24, No. 4. pp. 523-535.
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Glahn, DC, Nimgaonkar, VL, Raventos, H, McCarthy, N, Jablensky, A, Curran, JE, Almasy, L & Blangero, J 2019, 'Rediscovering the value of families for psychiatric genetics research' Molecular Psychiatry, vol. 24, no. 4, pp. 523-535. https://doi.org/10.1038/s41380-018-0073-x

Rediscovering the value of families for psychiatric genetics research. / Glahn, David C.; Nimgaonkar, V.L.; Raventos, H.; McCarthy, Nina; Jablensky, Assen; Curran, Joanne E.; Almasy, L; Blangero, John.

In: Molecular Psychiatry, Vol. 24, No. 4, 04.2019, p. 523-535.

Research output: Contribution to journalReview article

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AU - Glahn, David C.

AU - Nimgaonkar, V.L.

AU - Raventos, H.

AU - McCarthy, Nina

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AU - Curran, Joanne E.

AU - Almasy, L

AU - Blangero, John

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ER -