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Genetic associations of nonsynonymous exonic variants with psychophysiological endophenotypes

dc.contributor.authorVrieze, Scott I.en_US
dc.contributor.authorMalone, Stephen M.en_US
dc.contributor.authorPankratz, Nathanen_US
dc.contributor.authorVaidyanathan, Umaen_US
dc.contributor.authorMiller, Michael B.en_US
dc.contributor.authorKang, Hyun Minen_US
dc.contributor.authorMcGue, Matten_US
dc.contributor.authorAbecasis, Gonçaloen_US
dc.contributor.authorIacono, William G.en_US
dc.date.accessioned2014-12-09T16:53:53Z
dc.date.availableWITHHELD_13_MONTHSen_US
dc.date.available2014-12-09T16:53:53Z
dc.date.issued2014-12en_US
dc.identifier.citationVrieze, Scott I.; Malone, Stephen M.; Pankratz, Nathan; Vaidyanathan, Uma; Miller, Michael B.; Kang, Hyun Min; McGue, Matt; Abecasis, Gonçalo ; Iacono, William G. (2014). "Genetic associations of nonsynonymous exonic variants with psychophysiological endophenotypes." Psychophysiology (12): 1300-1308.en_US
dc.identifier.issn0048-5772en_US
dc.identifier.issn1469-8986en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/109617
dc.description.abstractWe mapped ∼85,000 rare nonsynonymous exonic single nucleotide polymorphisms ( SNPs ) to 17 psychophysiological endophenotypes in 4,905 individuals, including antisaccade eye movements, resting EEG , P 300 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 PARD 3 gene associated with theta resting EEG power. The sequence kernel association test, a gene‐based test, identified a gene PNPLA 7 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.en_US
dc.publisherThe Center for Research in Psychophysiology, University of Floridaen_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherElectrodermalen_US
dc.subject.otherEEGen_US
dc.subject.otherStartleen_US
dc.subject.otherEndophenotypeen_US
dc.subject.otherPsychophysiologyen_US
dc.subject.otherExomeen_US
dc.subject.otherRare Varianten_US
dc.subject.otherNonsynonymousen_US
dc.subject.otherGWASen_US
dc.subject.otherP 300en_US
dc.subject.otherAntisaccadeen_US
dc.titleGenetic associations of nonsynonymous exonic variants with psychophysiological endophenotypesen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelPsychologyen_US
dc.subject.hlbsecondlevelPhysiologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/109617/1/psyp12349.pdf
dc.identifier.doi10.1111/psyp.12349en_US
dc.identifier.sourcePsychophysiologyen_US
dc.identifier.citedreferenceRichardson, R. J., Hein, N. D., Wijeyesakere, S. J., Fink, J. K., & Makhaeva, G. F. ( 2013 ). Neuropathy target esterase (NTE): Overview and future. Chemico‐Biological Interactions, 203, 238 – 244. doi: 10.1016/j.cbi.2012.10.024en_US
dc.identifier.citedreferenceHarrow, J., Frankish, A., Gonzalez, J. M., Tapanari, E., Diekhans, M., Kokocinski, F., … Hubbard, T. J. ( 2012 ). GENCODE: The reference human genome annotation for The ENCODE Project. Genome Research, 22, 1760 – 1774. doi: 10.1101/gr.135350.111en_US
dc.identifier.citedreferenceIacono, W. G., Malone, S. M., Vaidyanathan, U., & Vrieze, S. I. ( 2014 ). Genome‐wide scans of genetic variants for psychophysiological endophenotypes: A methodological overview. Psychophysiology, 51, 1207 – 1224.en_US
dc.identifier.citedreferenceIacono, W. G., & McGue, M. ( 2002 ). Minnesota Twin Family Study. Twin Research and Human Genetics, 5, 482 – 487.en_US
dc.identifier.citedreferenceIacono, W. G., McGue, M., & Krueger, R. F. ( 2006 ). Minnesota Center for Twin and Family Research. Twin Research and Human Genetics, 9, 978 – 984. doi: 10.1375/183242706779462642en_US
dc.identifier.citedreferenceKang, H. M. ( 2014 ). Efficient and Parallelizable Association Container Toolbox (EPACTS). Retrieved from http://genome.sph.umich.edu/wiki/EPACTSen_US
dc.identifier.citedreferenceKang, H. M., Sul, J. H., Service, S. K., Zaitlen, N. A., Kong, S. Y., Freimer, N. B., … Eskin, E. ( 2010 ). Variance component model to account for sample structure in genome‐wide association studies. Nature Genetics, 42, 348 – 354. doi: 10.1038/Ng.548en_US
dc.identifier.citedreferenceKeyes, M. A., Malone, S. M., Elkins, I. J., Legrand, L. N., McGue, M., & Iacono, W. G. ( 2009 ). The enrichment study of the Minnesota Twin Family Study: Increasing the yield of twin families at high risk for externalizing psychopathology. Twin Research and Human Genetics, 12, 489 – 501. doi: 10.1375/twin.12.5.489en_US
dc.identifier.citedreferenceKim, S. K., Lee, J. Y., Park, H. J., Kim, J. W., & Chung, J.‐H. ( 2012 ). Association study between polymorphisms of the PARD3 gene and schizophrenia. Experimental and Therapeutic Medicine, 3, 881 – 885.en_US
dc.identifier.citedreferenceKircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. ( 2014 ). A general framework for estimating the relative pathogenicity of human genetic variants. Nature Genetics, 46, 310 – 315. doi: 10.1038/ng.2892en_US
dc.identifier.citedreferenceKumar, P., Henikoff, S., & Ng, P. C. ( 2009 ). Predicting the effects of coding non‐synonymous variants on protein function using the SIFT algorithm. Nature Protocols, 4, 1073 – 1081. doi: 10.1038/nprot.2009.86en_US
dc.identifier.citedreferenceLang, P. J., Bradley, M. M., & Cuthbert, B. N. ( 1999 ). International affective picture system (IAPS): Technical manual and affective ratings. Gainesville, FL: The Center for Research in Psychophysiology, University of Florida.en_US
dc.identifier.citedreferenceLee, S., Abecasis, G. R., Boehnke, M., & Lin, X. ( 2014 ). Rare‐variant association analysis: Study designs and statistical tests. American Journal of Human Genetics, 95, 5 – 23. doi: 10.1016/j.ajhg.2014.06.009en_US
dc.identifier.citedreferenceLi, B. S., & Leal, S. M. ( 2008 ). Methods for detecting associations with rare variants for common diseases: Application to analysis of sequence data. American Journal of Human Genetics, 83, 311 – 321. doi: 10.1016/j.ajhg.2008.06.024en_US
dc.identifier.citedreferenceListgarten, J., Lippert, C., Kadie, C. M., Davidson, R. I., Eskin, E., & Heckerman, D. ( 2012 ). Improved linear mixed models for genome‐wide association studies. Nature Methods, 9, 525 – 526. doi: 10.1038/nmeth.2037en_US
dc.identifier.citedreferenceMalone, S. M., Burwell, S. J., Vaidyanathan, U., Miller, M. B., McGue, M., & Iacono, W. G. ( 2014 ). Heritability and molecular genetic basis of resting EEG activity: A genome‐wide association study. Psychophysiology, 51, 1225 – 1245.en_US
dc.identifier.citedreferenceMalone, S. M., Vaidyanathan, U., Basu, S., Miller, M. B., McGue, M., & Iacono, W. G. ( 2014 ). Heritability and molecular genetic basis of P3 event‐related brain potential amplitude: A genome‐wide association study. Psychophysiology, 51, 1246 – 1258.en_US
dc.identifier.citedreferenceMcLaren, W., Pritchard, B., Rios, D., Chen, Y. A., Flicek, P., & Cunningham, F. ( 2010 ). Deriving the consequences of genomic variants with the ensembl API and SNP effect predictor. Bioinformatics, 26, 2069 – 2070. doi: 10.1093/bioinformatics/btq330en_US
dc.identifier.citedreferenceMiller, M. B., Basu, S., Cunningham, J., Eskin, E., Malone, S. M., Oetting, W. S., … McGue, M. ( 2012 ). The Minnesota Center for Twin and Family Research genome‐wide association study. Twin Research and Human Genetics, 15, 767 – 774.en_US
dc.identifier.citedreferencePankratz, N. ( 2014 ). Genetic visualization with GENVISIS. Manuscript in preparation.en_US
dc.identifier.citedreferencePrice, A. L., Kryukov, G. V., de Bakker, P. I., Purcell, S. M., Staples, J., Wei, L. J., & Sunyaev, S. R. ( 2010 ). Pooled association tests for rare variants in exon‐resequencing studies. American Journal of Human Genetics, 86, 832 – 838. doi: 10.1016/j.ajhg.2010.04.005en_US
dc.identifier.citedreferenceRangaswamy, M., Porjesz, B., Chorlian, D. B., Choi, K., Jones, K. A., Wang, K., … Begleiter, H. ( 2003 ). Theta power in the EEG of alcoholics. Alcoholism, Clinical and Experimental Research, 27, 607 – 615. doi: 10.1097/01.ALC.0000060523.95470.8Fen_US
dc.identifier.citedreferenceSponheim, S. R., Clementz, B. A., Iacono, W. G., & Beiser, M. ( 1994 ). Resting EEG in first‐episode and chronic schizophrenia. Psychophysiology, 31, 37 – 43.en_US
dc.identifier.citedreferenceSponheim, S. R., Clementz, B. A., Iacono, W. G., & Beiser, M. ( 2000 ). Clinical and biological concomitants of resting state EEG power abnormalities in schizophrenia. Biological Psychiatry, 48, 1088 – 1097.en_US
dc.identifier.citedreferenceSponheim, S. R., Iacono, W. G., Thuras, P. D., Nugent, S. M., & Beiser, M. ( 2003 ). Sensitivity and specificity of select biological indices in characterizing psychotic patients and their relatives. Schizophrenia Research, 63, 27 – 38.en_US
dc.identifier.citedreferenceStein, J. L., Medland, S. E., Vasquez, A. A., Hibar, D. P., Senstad, R. E., Winkler, A. M., … Thompson, P. M. ( 2012 ). Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics, 44, 552 – 561.en_US
dc.identifier.citedreferenceStruve, F. A., Straumanis, J. J., Patrick, G., Leavitt, J., Manno, J. E., & Manno, B. R. ( 1999 ). Topographic quantitative EEG sequelae of chronic marihuana use: A replication using medically and psychiatrically screened normal subjects. Drug and Alcohol Dependence, 56, 167 – 179.en_US
dc.identifier.citedreferenceTennessen, J. A., Bigham, A. W., O'Connor, T. D., Fu, W., Kenny, E. E., Gravel, S., … NHLBI Exome Sequencing Project. ( 2012 ). Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science, 337, 64 – 69. doi: 10.1126/science.1219240en_US
dc.identifier.citedreferenceThompson, P. M., Stein, J. L., Medland, S. E., Hibar, D. P., Vasquez, A. A., Renteria, M. E., … Drevets, W. ( 2014 ). The ENIGMA Consortium: Large‐scale collaborative analyses of neuroimaging and genetic data. Brain Imaging and Behavior, 1 – 30. doi: 10.1007/s11682‐013‐9269‐5en_US
dc.identifier.citedreferenceVaidyanathan, U., Isen, J. D., Malone, S. M., Miller, M. B., McGue, M., & Iacono, W. G. ( 2014 ). Heritability and molecular genetic basis of electrodermal activity: A genome‐wide association study. Psychophysiology, 51, 1259 – 1271.en_US
dc.identifier.citedreferenceVaidyanathan, U., Malone, S. M., Donnelly, J. M., Hammer, M. A., Miller, M. B., McGue, M., & Iacono, W. G. ( 2014 ). Heritability and molecular genetic basis of antisaccade eye tracking error rate: A genome‐wide association study. Psychophysiology, 51, 1272 – 1284.en_US
dc.identifier.citedreferenceVaidyanathan, U., Malone, S. M., Miller, M. B., McGue, M., & Iacono, W. G. ( 2014 ). Heritability and molecular genetic basis of acoustic startle eye blink and affectively modulated startle response: A genome‐wide association study. Psychophysiology, 51, 1285 – 1299.en_US
dc.identifier.citedreferenceVrieze, S. I., Malone, S. M., Vaidyanathan, U., Kwong, A., Kang, H. M., Zhan, X., … Iacono, W. G. ( 2014 ). In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes. Psychophysiology, 51, 1309 – 1320.en_US
dc.identifier.citedreferenceWilson, P. A., Gardner, S. D., Lambie, N. M., Commans, S. A., & Crowther, D. J. ( 2006 ). Characterization of the human patatin‐like phospholipase family. Journal of Lipid Research, 47, 1940 – 1949. doi: 10.1194/jlr.M600185‐JLR200en_US
dc.identifier.citedreferenceWu, M. C., Lee, S., Cai, T. X., Li, Y., Boehnke, M., & Lin, X. H. ( 2011 ). Rare‐variant association testing for sequencing data with the sequence kernel association test. American Journal of Human Genetics, 89, 82 – 93. doi: 10.1016/j.ajhg.2011.05.029en_US
dc.identifier.citedreferenceAdzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., … Sunyaev, S. R. ( 2010 ). A method and server for predicting damaging missense mutations. Nature Methods, 7, 248 – 249. doi: 10.1038/nmeth0410‐248en_US
dc.identifier.citedreferenceAsimit, J., & Zeggini, E. ( 2010 ). Rare variant association analysis methods for complex traits. Annual Review of Genetics, 44, 293 – 308. doi: 10.1146/annurev‐genet‐102209‐163421en_US
dc.identifier.citedreferenceBarry, R. J., Clarke, A. R., & Johnstone, S. J. ( 2003 ). A review of electrophysiology in attention‐deficit/hyperactivity disorder: I. Qualitative and quantitative electroencephalography. Clinical Neurophysiology, 114, 171 – 183.en_US
dc.identifier.citedreferenceBegic, D., Popovic‐Knapic, V., Grubisin, J., Kosanovic‐Rajacic, B., Filipcic, I., Telarovic, I., & Jakovljevic, M. ( 2011 ). Quantitative electroencephalography in schizophrenia and depression. Psychiatria Danubina, 23, 355 – 362.en_US
dc.identifier.citedreferenceClementz, B. A., Sponheim, S. R., Iacono, W. G., & Beiser, M. ( 1994 ). Resting EEG in first‐episode schizophrenia patients, bipolar psychosis patients, and their first‐degree relatives. Psychophysiology, 31, 486 – 494.en_US
dc.identifier.citedreferenceEhlers, C. L., Phillips, E., Gizer, I. R., Gilder, D. A., & Wilhelmsen, K. C. ( 2010 ). EEG spectral phenotypes: Heritability and association with marijuana and alcohol dependence in an American Indian community study. Drug and Alcohol Dependence, 106, 101 – 110. doi: 10.1016/j.drugalcdep.2009.07.024en_US
dc.identifier.citedreferenceGottesman, I. I., & Gould, T. D. ( 2003 ). The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry, 160, 636 – 645.en_US
dc.identifier.citedreferenceHarris, A., Melkonian, D., Williams, L., & Gordon, E. ( 2006 ). Dynamic spectral analysis findings in first episode and chronic schizophrenia. International Journal of Neuroscience, 116, 223 – 246. doi: 10.1080/00207450500402977en_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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