The genomics of major psychiatric disorders in a large pedigree from Northern Sweden

被引:13
作者
Szatkiewicz, Jin [1 ]
Crowley, James J. [1 ]
Adolfsson, Annelie Nordin [2 ]
Aberg, Karolina A. [3 ]
Alaerts, Maaike [4 ,5 ]
Genovese, Giulio [6 ]
McCarroll, Steven [6 ]
Del-Favero, Jurgen [7 ,8 ]
Adolfsson, Rolf [2 ]
Sullivan, Patrick F. [1 ,9 ,10 ]
机构
[1] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA
[2] Univ Umea, Dept Clin Sci & Psychiat, Umea, Sweden
[3] Virginia Commonwealth Univ, Ctr Biomarker Res & Precis Med, Richmond, VA USA
[4] Univ Antwerp, Ctr Med Genet, Antwerp, Belgium
[5] Antwerp Univ Hosp, Antwerp, Belgium
[6] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
[7] VIB Ctr Mol Neurol, Univ Pl 1, Antwerp, Belgium
[8] Multiplicom NV, Galileilaan 18, Niel, Belgium
[9] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA
[10] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden
基金
瑞典研究理事会;
关键词
COPY NUMBER VARIATION; BIPOLAR DISORDER; ASSOCIATION; SCHIZOPHRENIA; INTERVIEW;
D O I
10.1038/s41398-019-0414-9
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
We searched for genetic causes of major psychiatric disorders (bipolar disorder, schizoaffective disorder, and schizophrenia) in a large, densely affected pedigree from Northern Sweden that originated with three pairs of founders born around 1650. We applied a systematic genomic approach to the pedigree via karyotyping (N = 9), genome-wide SNP arrays (N = 418), whole-exome sequencing (N = 26), and whole-genome sequencing (N = 10). Comprehensive analysis did not identify plausible variants of strong effect. Rather, pedigree cases had significantly higher genetic risk scores compared to pedigree and community controls.
引用
收藏
页数:8
相关论文
共 41 条
[1]   Genetic effects on gene expression across human tissues [J].
Aguet, Francois ;
Brown, Andrew A. ;
Castel, Stephane E. ;
Davis, Joe R. ;
He, Yuan ;
Jo, Brian ;
Mohammadi, Pejman ;
Park, Yoson ;
Parsana, Princy ;
Segre, Ayellet V. ;
Strober, Benjamin J. ;
Zappala, Zachary ;
Cummings, Beryl B. ;
Gelfand, Ellen T. ;
Hadley, Kane ;
Huang, Katherine H. ;
Lek, Monkol ;
Li, Xiao ;
Nedzel, Jared L. ;
Nguyen, Duyen Y. ;
Noble, Michael S. ;
Sullivan, Timothy J. ;
Tukiainen, Taru ;
MacArthur, Daniel G. ;
Getz, Gad ;
Management, Nih Program ;
Addington, Anjene ;
Guan, Ping ;
Koester, Susan ;
Little, A. Roger ;
Lockhart, Nicole C. ;
Moore, Helen M. ;
Rao, Abhi ;
Struewing, Jeffery P. ;
Volpi, Simona ;
Collection, Biospecimen ;
Brigham, Lori E. ;
Hasz, Richard ;
Hunter, Marcus ;
Johns, Christopher ;
Johnson, Mark ;
Kopen, Gene ;
Leinweber, William F. ;
Lonsdale, John T. ;
McDonald, Alisa ;
Mestichelli, Bernadette ;
Myer, Kevin ;
Roe, Bryan ;
Salvatore, Michael ;
Shad, Saboor .
NATURE, 2017, 550 (7675) :204-+
[2]   DSM-III-R psychotic disorders: procedural validity of the Mini International Neuropsychiatric Interview (MINI). Concordance and causes for discordance with the CIDI [J].
Amorim, P ;
Lecrubier, Y ;
Weiller, E ;
Hergueta, T ;
Sheehan, D .
EUROPEAN PSYCHIATRY, 1998, 13 (01) :26-34
[3]   Translating genome-wide association findings into new therapeutics for psychiatry [J].
Breen, Gerome ;
Li, Qingqin ;
Roth, Bryan L. ;
O'Donnell, Patricio ;
Didriksen, Michael ;
Dolmetsch, Ricardo ;
O'Reilly, Paul F. ;
Gaspar, Helena A. ;
Manji, Husseini ;
Huebel, Christopher ;
Kelsoe, John R. ;
Malhotra, Dheeraj ;
Bertolino, Alessandro ;
Posthuma, Danielle ;
Sklar, Pamela ;
Kapur, Shitij ;
Sullivan, Patrick F. ;
Collier, David A. ;
Edenberg, Howard J. .
NATURE NEUROSCIENCE, 2016, 19 (11) :1392-1396
[4]   Improving the Accuracy and Efficiency of Identity-by-Descent Detection in Population Data [J].
Browning, Brian L. ;
Browning, Sharon R. .
GENETICS, 2013, 194 (02) :459-+
[5]   Identifying bipolar disorder susceptibility loci in a densely affected pedigree [J].
Collins, A. L. ;
Kim, Y. ;
Szatkiewicz, J. P. ;
Bloom, R. J. ;
Hilliard, C. E. ;
Quackenbush, C. R. ;
Meier, S. ;
Rivas, F. ;
Mayoral, F. ;
Cichon, S. ;
Noethen, M. M. ;
Rietschel, M. ;
Sullivan, P. F. .
MOLECULAR PSYCHIATRY, 2013, 18 (12) :1245-1246
[6]   Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder [J].
de Jong, Simone ;
Abdalla Diniz, Mateus Jose ;
Saloma, Andiara ;
Gadelha, Ary ;
Santoro, Marcos L. ;
Ota, Vanessa K. ;
Noto, Cristiano ;
Curtis, Charlesg ;
Newhouse, Stephen J. ;
Patel, Hamel ;
Hall, Lynsey S. ;
O'Reilly, Paul F. ;
Belangero, Sintia, I ;
Bressan, Rodrigo A. ;
Breen, Gerome ;
Wray, Naomi R. ;
Ripke, Stephan ;
Mattheisen, Manuel ;
Trzaskowski, Maciej ;
Byrne, Enda M. ;
Abdellaoui, Abdel ;
Adams, Mark J. ;
Agerbo, Esben ;
Air, Tracy M. ;
Andlauer, Till F. M. ;
Bacanu, Silviu-Alin ;
Baekvad-Hansen, Marie ;
Beekman, Aartjan T. F. ;
Bigdeli, Tim B. ;
Binder, Elisabeth B. ;
Blackwood, Douglas H. R. ;
Bryois, Julien ;
Buttenschon, Henriette N. ;
Bybjerg-Grauholm, Jonas ;
Cai, Na ;
Castelao, Enrique ;
Christensen, Jane Hvarregaard ;
Clarke, Toni-Kim ;
Coleman, Jonathan R., I ;
Colodro-Conde, Lucia ;
Couvy-Duchesne, Baptiste ;
Craddock, Nick ;
Crawford, Gregory E. ;
Davies, Gail ;
Deary, Ian J. ;
Degenhardt, Franziska ;
Derks, Eske M. ;
Direk, Nese ;
Dolan, Conor, V ;
Dunn, Erin C. .
COMMUNICATIONS BIOLOGY, 2018, 1
[7]   Detection of long repeat expansions from PCR-free whole-genome sequence data [J].
Dolzhenko, Egor ;
van Vugt, Joke J. F. A. ;
Shaw, Richard J. ;
Bekritsky, Mitchell A. ;
van Blitterswijk, Marka ;
Narzisi, Giuseppe ;
Ajay, Subramanian S. ;
Rajan, Vani ;
Lajoie, Bryan R. ;
Johnson, Nathan H. ;
Kingsbury, Zoya ;
Humphray, Sean J. ;
Schellevis, Raymond D. ;
Brands, William J. ;
Baker, Matt ;
Rademakers, Rosa ;
Kooyman, Maarten ;
Tazelaar, Gijs H. P. ;
van Es, Michael A. ;
McLaughlin, Russell ;
Sproviero, William ;
Shatunov, Aleksey ;
Jones, Ashley ;
Al Khleifat, Ahmad ;
Pittman, Alan ;
Morgan, Sarah ;
Hardiman, Orla ;
Al-Chalabi, Ammar ;
Shaw, Chris ;
Smith, Bradley ;
Neo, Edmund J. ;
Morrison, Karen ;
Shaw, Pamela J. ;
Reeves, Catherine ;
Winterkorn, Lara ;
Wexler, Nancy S. ;
Housman, David E. ;
Ng, Christopher W. ;
Li, Alina L. ;
Taft, Ryan J. ;
van den Berg, Leonard H. ;
Bentley, David R. ;
Veldink, Jan H. ;
Eberle, Michael A. .
GENOME RESEARCH, 2017, 27 (11) :1895-1903
[8]   Developmental Delay, Treatment-Resistant Psychosis, and Early-Onset Dementia in a Man With 22q11 Deletion Syndrome and Huntington's Disease [J].
Farrell, Martilias ;
Lichtenstein, Maya ;
Crowley, James J. ;
Filmyer, Dawn M. ;
Lazaro-Munoz, Gabriel ;
Shaughnessy, Rita A. ;
Mackenzie, Ian R. ;
Hirsch-Reinshagen, Veronica ;
Stowe, Robert ;
Evans, James P. ;
Berg, Jonathan S. ;
Szatkiewicz, Jin ;
Josiassen, Richard C. ;
Sullivan, Patrick F. .
AMERICAN JOURNAL OF PSYCHIATRY, 2018, 175 (05) :400-407
[9]   Partitioning heritability by functional annotation using genome-wide association summary statistics [J].
Finucane, Hilary K. ;
Bulik-Sullivan, Brendan ;
Gusev, Alexander ;
Trynka, Gosia ;
Reshef, Yakir ;
Loh, Po-Ru ;
Anttila, Verneri ;
Xu, Han ;
Zang, Chongzhi ;
Farh, Kyle ;
Ripke, Stephan ;
Day, Felix R. ;
Purcell, Shaun ;
Stahl, Eli ;
Lindstrom, Sara ;
Perry, John R. B. ;
Okada, Yukinori ;
Raychaudhuri, Soumya ;
Daly, Mark J. ;
Patterson, Nick ;
Neale, Benjamin M. ;
Price, Alkes L. .
NATURE GENETICS, 2015, 47 (11) :1228-+
[10]  
FRANCES A, 1994, ARCH GEN PSYCHIAT, V51, P863