In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes

Scott I. Vrieze; Stephen M. Malone; Uma Vaidyanathan; Alan Kwong; Hyun Min Kang; Xiaowei Zhan; Matthew Flickinger; Daniel Irons; Goo Jun; Adam Locke; Giorgio Pistis; Eleonora Porcu; Shawn Levy; Richard M. Myers; William Oetting; Matt Mcgue; Goncalo Abecasis; William G. Iacono

doi:10.1111/psyp.12350

In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes

Scott I. Vrieze, Stephen M. Malone, Uma Vaidyanathan, Alan Kwong, Hyun Min Kang, Xiaowei Zhan, Matthew Flickinger, Daniel Irons, Goo Jun, Adam Locke, Giorgio Pistis, Eleonora Porcu, Shawn Levy, Richard M. Myers, William Oetting, Matt Mcgue, Goncalo Abecasis, William G. Iacono

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Abstract

Whole genome sequencing was completed on 1,325 individuals from 602 families, identifying 27 million autosomal variants. Genetic association tests were conducted for those individuals who had been assessed for one or more of 17 endophenotypes (N range=802-1,185). No significant associations were found. These 27 million variants were then imputed into the full sample of individuals with psychophysiological data (N range=3,088-4,469) and again tested for associations with the 17 endophenotypes. No association was significant. Using a gene-based variable threshold burden test of nonsynonymous variants, we obtained five significant associations. These findings are preliminary and call for additional analysis of this rich sample. We argue that larger samples, alternative study designs, and additional bioinformatics approaches will be necessary to discover associations between these endophenotypes and genomic variation.

Original language	English
Pages (from-to)	1309-1320
Number of pages	12
Journal	Psychophysiology
Volume	51
Issue number	12
DOIs	https://doi.org/10.1111/psyp.12350
State	Published - Dec 1 2014

Keywords

Antisaccade
EEG
Endophenotype
P300
Psychophysiology
Rare variant
Startle
Whole genome sequencing

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10.1111/psyp.12350

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Vrieze, S. I., Malone, S. M., Vaidyanathan, U., Kwong, A., Kang, H. M., Zhan, X., Flickinger, M., Irons, D., Jun, G., Locke, A., Pistis, G., Porcu, E., Levy, S., Myers, R. M., Oetting, W., Mcgue, M., Abecasis, G., & Iacono, W. G. (2014). In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes. Psychophysiology, 51(12), 1309-1320. https://doi.org/10.1111/psyp.12350

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title = "In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes",

abstract = "Whole genome sequencing was completed on 1,325 individuals from 602 families, identifying 27 million autosomal variants. Genetic association tests were conducted for those individuals who had been assessed for one or more of 17 endophenotypes (N range=802-1,185). No significant associations were found. These 27 million variants were then imputed into the full sample of individuals with psychophysiological data (N range=3,088-4,469) and again tested for associations with the 17 endophenotypes. No association was significant. Using a gene-based variable threshold burden test of nonsynonymous variants, we obtained five significant associations. These findings are preliminary and call for additional analysis of this rich sample. We argue that larger samples, alternative study designs, and additional bioinformatics approaches will be necessary to discover associations between these endophenotypes and genomic variation.",

keywords = "Antisaccade, EEG, Endophenotype, P300, Psychophysiology, Rare variant, Startle, Whole genome sequencing",

author = "Vrieze, {Scott I.} and Malone, {Stephen M.} and Uma Vaidyanathan and Alan Kwong and Kang, {Hyun Min} and Xiaowei Zhan and Matthew Flickinger and Daniel Irons and Goo Jun and Adam Locke and Giorgio Pistis and Eleonora Porcu and Shawn Levy and Myers, {Richard M.} and William Oetting and Matt Mcgue and Goncalo Abecasis and Iacono, {William G.}",

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Vrieze, SI, Malone, SM, Vaidyanathan, U, Kwong, A, Kang, HM, Zhan, X, Flickinger, M, Irons, D, Jun, G, Locke, A, Pistis, G, Porcu, E, Levy, S, Myers, RM, Oetting, W, Mcgue, M, Abecasis, G & Iacono, WG 2014, 'In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes', Psychophysiology, vol. 51, no. 12, pp. 1309-1320. https://doi.org/10.1111/psyp.12350

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AU - Kang, Hyun Min

AU - Zhan, Xiaowei

AU - Flickinger, Matthew

AU - Irons, Daniel

AU - Jun, Goo

AU - Locke, Adam

AU - Pistis, Giorgio

AU - Porcu, Eleonora

AU - Levy, Shawn

AU - Myers, Richard M.

AU - Oetting, William

AU - Mcgue, Matt

AU - Abecasis, Goncalo

AU - Iacono, William G.

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In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes

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Keywords

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