View Item 

Show simple item record

In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes
dc.contributor.authorVrieze, Scott I.en_US
dc.contributor.authorMalone, Stephen M.en_US
dc.contributor.authorVaidyanathan, Umaen_US
dc.contributor.authorKwong, Alanen_US
dc.contributor.authorKang, Hyun Minen_US
dc.contributor.authorZhan, Xiaoweien_US
dc.contributor.authorFlickinger, Matthewen_US
dc.contributor.authorIrons, Danielen_US
dc.contributor.authorJun, Gooen_US
dc.contributor.authorLocke, Adam E.en_US
dc.contributor.authorPistis, Giorgioen_US
dc.contributor.authorPorcu, Eleonoraen_US
dc.contributor.authorLevy, Shawnen_US
dc.contributor.authorMyers, Richard M.en_US
dc.contributor.authorOetting, Williamen_US
dc.contributor.authorMcGue, Matten_US
dc.contributor.authorAbecasis, Goncaloen_US
dc.contributor.authorIacono, William G.en_US
dc.date.accessioned2014-12-09T16:53:57Z
dc.date.availableWITHHELD_13_MONTHSen_US
dc.date.available2014-12-09T16:53:57Z
dc.date.issued2014-12en_US
dc.identifier.citationVrieze, Scott I.; Malone, Stephen M.; Vaidyanathan, Uma; Kwong, Alan; Kang, Hyun Min; Zhan, Xiaowei; Flickinger, Matthew; Irons, Daniel; Jun, Goo; Locke, Adam E.; Pistis, Giorgio; Porcu, Eleonora; Levy, Shawn; Myers, Richard M.; Oetting, William; McGue, Matt; Abecasis, Goncalo; Iacono, William G. (2014). "In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes." Psychophysiology (12): 1309-1320.en_US
dc.identifier.issn0048-5772en_US
dc.identifier.issn1469-8986en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/109628
dc.description.abstractWhole 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.en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherWhole Genome Sequencingen_US
dc.subject.otherPsychophysiologyen_US
dc.subject.otherEndophenotypeen_US
dc.subject.otherEEGen_US
dc.subject.otherAntisaccadeen_US
dc.subject.otherStartleen_US
dc.subject.otherP300en_US
dc.subject.otherRare Varianten_US
dc.titleIn search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypesen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelPhysiologyen_US
dc.subject.hlbsecondlevelPsychologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/109628/1/psyp12350.pdf
dc.identifier.doi10.1111/psyp.12350en_US
dc.identifier.sourcePsychophysiologyen_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.citedreferenceBevilacqua, L., Doly, S., Kaprio, J., Yuan, Q., Tikkanen, R., Paunio, T., … Goldman, D. ( 2010 ). A population‐specific HTR2B stop codon predisposes to severe impulsivity. Nature, 468, 1061 – 1066. doi: 10.1038/nature09629en_US
dc.identifier.citedreferenceBrowning, B. L., & Browning, S. R. ( 2009 ). A unified approach to genotype imputation and haplotype‐phase inference for large data sets of trios and unrelated individuals. American Journal of Human Genetics, 84, 210 – 223.en_US
dc.identifier.citedreferenceCock, P. J., Fields, C. J., Goto, N., Heuer, M. L., & Rice, P. M. ( 2010 ). The Sanger FASTQ file format for sequences with quality scores, and the Solexa/Illumina FASTQ variants. Nucleic Acids Research, 38, 1767 – 1771.en_US
dc.identifier.citedreferenceDelaneau, O., Zagury, J. F., & Marchini, J. ( 2013 ). Improved whole‐chromosome phasing for disease and population genetic studies. Nature Methods, 10, 5 – 6. doi: 10.1038/nmeth.2307en_US
dc.identifier.citedreferenceENCODE Project Consortium. ( 2012 ). An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57 – 74. doi: 10.1038/nature11247en_US
dc.identifier.citedreferenceFromer, M., Pocklington, A. J., Kavanagh, D. H., Williams, H. J., Dwyer, S., Gormley, P., … O'Donovan, M. C. ( 2014 ). De novo mutations in schizophrenia implicate synaptic networks. Nature, 506, 179 – 184. doi: 10.1038/nature12929en_US
dc.identifier.citedreferenceFu, W. Q., O'Connor, T. D., Jun, G., Kang, H. M., Abecasis, G., Leal, S. M., … NHLBI Exome Sequencing Project ( 2013 ). Analysis of 6,515 exomes reveals the recent origin of most human protein‐coding variants. Nature, 493, 216 – 220. doi: 10.1038/Nature11690en_US
dc.identifier.citedreferenceGlessner, J. T., Wang, K., Cai, G., Korvatska, O., Kim, C. E., Wood, S., Hakonarson, H. ( 2009 ). Autism genome‐wide copy number variation reveals ubiquitin and neuronal genes. Nature, 459, 569 – 573. doi: 10.1038/nature07953en_US
dc.identifier.citedreferenceHirschhorn, J. N., Lohmueller, K., Byrne, E., & Hirschhorn, K. ( 2002 ). A comprehensive review of genetic association studies. Genetics in Medicine, 4, 45 – 61.en_US
dc.identifier.citedreferenceHowie, B., Fuchsberger, C., Stephens, M., Marchini, J., & Abecasis, G. R. ( 2012 ). Fast and accurate genotype imputation in genome‐wide association studies through pre‐phasing. Nature Genetics, 44, 955 – 959. doi: 10.1038/ng.2354en_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.citedreferenceInsel, T. R., Cuthbert, B. N., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., … Wang, P. ( 2010 ). Research Domain Criteria (RDoC): Toward a new classification framework for research on mental disorders. American Journal of Psychiatry, 167, 748 – 751. doi: 10.1176/appi.ajp.2010.09091379en_US
dc.identifier.citedreferenceVisscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. ( 2012 ). Five years of GWAS discovery. American Journal of Human Genetics, 90, 7 – 24. doi: 10.1016/j.ajhg.2011.11.029en_US
dc.identifier.citedreferenceJun, G., Flickinger, M., Hetrick, K. N., Romm, J. M., Doheny, K. F., Abecasis, G. R., … Kang, H. M. ( 2012 ). Detecting and estimating contamination of human DNA samples in sequencing and array‐based genotype data. American Journal of Human Genetics, 91, 839 – 848.en_US
dc.identifier.citedreferenceJun, G., Wing, M. K., Abecasis, G. R., & Kang, H. M. ( 2014 ). An efficient and scalable analysis framework for variant extraction and refinement from population scale DNA sequence data. Manuscript in preparation.en_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.citedreferenceLander, E. S. ( 2011 ). Initial impact of the sequencing of the human genome. Nature, 470, 187 – 197. doi: 10.1038/nature09792en_US
dc.identifier.citedreferenceLi, H., & Durbin, R. ( 2010 ). Fast and accurate long‐read alignment with Burrows–Wheeler transform. Bioinformatics, 26, 589 – 595.en_US
dc.identifier.citedreferenceLi, Y., Willer, C. J., Ding, J., Scheet, P., & Abecasis, G. R. ( 2010 ). MaCH: Using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genetic Epidemiology, 34, 816 – 834. doi: 10.1002/Gepi.20533en_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.citedreferenceMaurano, M. T., Humbert, R., Rynes, E., Thurman, R. E., Haugen, E., Wang, H., … Stamatoyannopoulos, J. A. ( 2012 ). Systematic localization of common disease‐associated variation in regulatory DNA. Science, 337, 1190 – 1195. doi: 10.1126/science.1222794en_US
dc.identifier.citedreferenceMcGue, M., Zhang, Y., Miller, M. B., Basu, S., Vrieze, S., Hicks, B., … Iacono, W. G. ( 2013 ). A genome‐wide association study of behavioral disinhibition. Behavior Genetics, 43, 363 – 373.en_US
dc.identifier.citedreferenceNeale, B. M., Kou, Y., Liu, L., Ma'ayan, A., Samocha, K. E., Sabo, A., … Daly, M. J. ( 2012 ). Patterns and rates of exonic de novo mutations inautism spectrum disorders. Nature, 485, 242 – 245. doi: 10.1038/nature11011en_US
dc.identifier.citedreferenceNelson, M. R., Wegmann, D., Ehm, M. G., Kessner, D., St Jean, P., Verzilli, C., … Mooser, V. ( 2012 ). An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people. Science, 337, 100 – 104. doi: 10.1126/science.1217876en_US
dc.identifier.citedreferenceO'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., … Eichler, E. E. ( 2011 ). Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nature Genetics, 43, 585 – 589. doi: 10.1038/Ng.835en_US
dc.identifier.citedreferencePickrell, J. K. ( 2014 ). Joint analysis of functional genomic data and genome‐wide association studies of 18 human traits. American Journal of Human Genetics, 94, 559 – 573. doi: 10.1016/j.ajhg.2014.03.004en_US
dc.identifier.citedreferencePoduri, A., Evrony, G. D., Cai, X., & Walsh, C. A. ( 2013 ). Somatic mutation, genomic variation, and neurological disease. Science, 341, 1237758. doi: 10.1126/science.1237758en_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.citedreferencePurcell, S. M., Moran, J. L., Fromer, M., Ruderfer, D., Solovieff, N., Roussos, P., … Sklar, P. ( 2014 ). A polygenic burden of rare disruptive mutations in schizophrenia. Nature, 506, 185 – 190. doi: 10.1038/nature12975en_US
dc.identifier.citedreferenceRees, E., Walters, J. T., Chambert, K. D., O'Dushlaine, C., Szatkiewicz, J., Richards, A. L., … Kirov, G. ( 2014 ). CNV analysis in a large schizophrenia sample implicates deletions at 16p12.1 and SLC1A1 and duplications at 1p36.33 and CGNL1. Human Molecular Genetics, 23, 1669 – 1676. doi: 10.1093/hmg/ddt540en_US
dc.identifier.citedreferenceSullivan, P. F. ( 2007 ). Spurious genetic associations. Biological Psychiatry, 61, 1121 – 1126. doi: 10.1016/j.biopsych.2006.11.010en_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., Iacono, W. G., & McGue, M. ( 2012 ). Confluence of genes, environment, development, and behavior in a post genome‐wide association study world. Development and Psychopathology, 24, 1195 – 1214. doi: 10.1017/S0954579412000648en_US
dc.identifier.citedreferenceVrieze, S. I., Malone, S. M., Pankratz, N., Vaidyanathan, U., Miller, M. B., Kang, H. M., … Iacono, W. G. ( 2014 ). Genetic associations of nonsynonymous exonic variants with psychophysiological endophenotypes. Psychophysiology, 51, 1300 – 1308.en_US
dc.identifier.citedreferenceWu, M. C., Lee, S., Cai, T., Li, Y., Boehnke, M., & Lin, X. ( 2011 ). Rare‐variant association testing for sequencing data with the sequence kernel association test. American Journal of Human Genetics, 89, 82 – 93.en_US
dc.identifier.citedreference1000 Genomes Project Consortium. ( 2012 ). An integrated map of genetic variation from 1,092 human genomes. Nature, 491, 56 – 65. doi: 10.1038/nature11632en_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


Files in this item

Name:
psyp12350.pdf
Size:
442.3KB
Format:
PDF
View/Open

Show simple item record

Remediation of Harmful Language

The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.

Accessibility

If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.