Genetic associations of nonsynonymous exonic variants with psychophysiological endophenotypes

Scott I. Vrieze, Stephen M. Malone, Nathan Pankratz, Uma Vaidyanathan, Michael B. Miller, Hyun Min Kang, Matt Mcgue, Gonçalo Abecasis, William G. Iacono

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


We mapped ∼85,000 rare nonsynonymous exonic single nucleotide polymorphisms (SNPs) to 17 psychophysiological endophenotypes in 4,905 individuals, including antisaccade eye movements, resting EEG, P300 amplitude, electrodermal activity, affect-modulated startle eye blink. Nonsynonymous SNPs are predicted to directly change or disrupt proteins encoded by genes and are expected to have significant biological consequences. Most such variants are rare, and new technologies can efficiently assay them on a large scale. We assayed 247,870 mostly rare SNPs on an Illumina exome array. Approximately 85,000 of the SNPs were polymorphic, rare (MAF<.05), and nonsynonymous. Single variant association tests identified a SNP in the PARD3 gene associated with theta resting EEG power. The sequence kernel association test, a gene-based test, identified a gene PNPLA7 associated with pleasant difference startle, the difference in startle magnitude between pleasant and neutral images. No other single nonsynonymous variant, or gene-based group of variants, was strongly associated with any endophenotype.

Original languageEnglish (US)
Pages (from-to)1300-1308
Number of pages9
Issue number12
StatePublished - Dec 1 2014


  • Antisaccade
  • EEG
  • Electrodermal
  • Endophenotype
  • Exome
  • GWAS
  • Nonsynonymous
  • P300
  • Psychophysiology
  • Rare variant
  • Startle

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