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Rediscovering the value of families for psychiatric genetics research

Citation

Glahn, DC and Nimgaonkar, VL and Raventos, H and Contreras, J and McIntosh, AM and Thomson, PA and Jablensky, A and McCarthy, NS and Charlesworth, JC and Blackburn, NB and Peralta, JM and Knowles, EEM and Mathias, SR and Ament, SA and McMahon, FJ and Gur, RC and Bucan, M and Curran, JE and Almasy, L and Gur, RE and Blangero, J, Rediscovering the value of families for psychiatric genetics research, Molecular Psychiatry pp. 1-13. ISSN 1359-4184 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 Macmillan Publishers Limited, part of Springer Nature

DOI: doi:10.1038/s41380-018-0073-x

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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Neurogenetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
UTAS Author:Charlesworth, JC (Dr Jac Charlesworth)
ID Code:128041
Year Published:2018
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-08-29
Last Modified:2019-08-14
Downloads:0

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