[en] BACKGROUND: The 15q11.2 deletion is frequently identified in the neurodevelopmental clinic. Case-control studies have associated the 15q11.2 deletion with neurodevelopmental disorders, and clinical case series have attempted to delineate a microdeletion syndrome with considerable phenotypic variability. The literature on this deletion is extensive and confusing, which is a challenge for genetic counselling. The aim of this study was to estimate the effect size of the 15q11.2 deletion and quantify its contribution to neurodevelopmental disorders. METHODS: We performed meta-analyses on new and previously published case-control studies and used statistical models trained in unselected populations with cognitive assessments. We used new (n=241) and previously published (n=150) data from a clinically referred group of deletion carriers. 15q11.2 duplications (new n=179 and previously published n=35) were used as a neutral control variant. RESULTS: The deletion decreases IQ by 4.3 points. The estimated ORs and respective frequencies in deletion carriers for intellectual disabilities, schizophrenia and epilepsy are 1.7 (3.4%), 1.5 (2%) and 3.1 (2.1%), respectively. There is no increased risk for heart malformations and autism. In the clinically referred group, the frequency and nature of symptoms in deletions are not different from those observed in carriers of the 15q11.2 duplication suggesting that most of the reported symptoms are due to ascertainment bias. CONCLUSIONS: We recommend that the deletion should be classified as 'pathogenic of mild effect size'. Since it explains only a small proportion of the phenotypic variance in carriers, it is not worth discussing in the developmental clinic or in a prenatal setting.
Disciplines :
Genetics & genetic processes
Author, co-author :
Jonch, Aia Elise
Douard, Elise
Moreau, Clara
Van Dijck, Anke
Passeggeri, Marzia
Kooy, Frank
Puechberty, Jacques
Campbell, Carolyn
Sanlaville, Damien
Lefroy, Henrietta
Richetin, Sonia
Pain, Aurelie
Genevieve, David
Kini, Usha
Le Caignec, Cedric
Lespinasse, James
Skytte, Anne-Bine
Isidor, Bertrand
Zweier, Christiane
CABERG, Jean-Hubert ; Centre Hospitalier Universitaire de Liège - CHU > Unilab > Unité de laboratoire - neurogénétique
D'Angelo D, Lebon S, Chen Q, Martin-Brevet S, Snyder LG, Hippolyte L, Hanson E, Maillard AM, Faucett WA, Macé A, Pain A, Bernier R, Chawner SJRA, David A, Andrieux J, Aylward E, Baujat G, Caldeira I, Conus P, Ferrari C, Forzano F, Gérard M, Goin-Kochel RP, Grant E, Hunter JV, Isidor B, Jacquette A, Jønch AE, Keren B, Lacombe D, Le Caignec C, Martin CL, Männik K, Metspalu A, Mignot C, Mukherjee P, Owen MJ, Passeggeri M, Rooryck-Thambo C, Rosenfeld JA, Spence SJ, Steinman KJ, Tjernagel J, Van Haelst M, Shen Y, Draganski B, Sherr EH, Ledbetter DH, van den Bree MBM, Beckmann JS, Spiro JE, Reymond A, Jacquemont S, Chung WK, Cardiff University Experiences of Children With Copy Number Variants (ECHO) Study, 16p11. 2 European Consortium, Simons Variation in Individuals Project (VIP) Consortium. Defining the effect of the 16p11. 2 duplication on cognition, behavior, and medical comorbidities. JAMA Psychiatry 2016;73:20-30.
Marshall CR, Howrigan DP, Merico D, Thiruvahindrapuram B, Wu W, Greer DS, Antaki D, Shetty A, Holmans PA, Pinto D, Gujral M, Brandler WM, Malhotra D, Wang Z, Fajarado KVF, Maile MS, Ripke S, Agartz I, Albus M, Alexander M, Amin F, Atkins J, Bacanu SA, Belliveau RA, Bergen SE, Bertalan M, Bevilacqua E, Bigdeli TB, Black DW, Bruggeman R, Buccola NG, Buckner RL, Bulik-Sullivan B, Byerley W, Cahn W, Cai G, Cairns MJ, Campion D, Cantor RM, Carr VJ, Carrera N, Catts SV, Chambert KD, Cheng W, Cloninger CR, Cohen D, Cormican P, Craddock N, Crespo-Facorro B, Crowley JJ, Curtis D, Davidson M, Davis KL, Degenhardt F, Del Favero J, DeLisi LE, Dikeos D, Dinan T, Djurovic S, Donohoe G, Drapeau E, Duan J, Dudbridge F, Eichhammer P, Eriksson J, Escott-Price V, Essioux L, Fanous AH, Farh K-H, Farrell MS, Frank J, Franke L, Freedman R, Freimer NB, Friedman JI, Forstner AJ, Fromer M, Genovese G, Georgieva L, Gershon ES, Giegling I, Giusti-Rodríguez P, Godard S, Goldstein JI, Gratten J, de Haan L, Hamshere ML, Hansen M, Hansen T, Haroutunian V, Hartmann AM, Henskens FA, Herms S, Hirschhorn JN, Hoffmann P, Hofman A, Huang H, Ikeda M, Joa I, Kähler AK, Kahn RS, Kalaydjieva L, Karjalainen J, Kavanagh D, Keller MC, Kelly BJ, Kennedy JL, Kim Y, Knowles JA, Konte B, Laurent C, Lee P, Lee SH, Legge SE, Lerer B, Levy DL, Liang K-Y, Lieberman J, Lönnqvist J, Loughland CM, Magnusson PKE, Maher BS, Maier W, Mallet J, Mattheisen M, Mattingsdal M, McCarley RW, McDonald C, McIntosh AM, Meier S, Meijer CJ, Melle I, Mesholam-Gately RI, Metspalu A, Michie PT, Milani L, Milanova V, Mokrab Y, Morris DW, Müller-Myhsok B, Murphy KC, Murray RM, Myin-Germeys I, Nenadic I, Nertney DA, Nestadt G, Nicodemus KK, Nisenbaum L, Nordin A, O'Callaghan E, O'Dushlaine C, Oh S-Y, Olincy A, Olsen L, O'Neill FA, Van Os J, Pantelis C, Papadimitriou GN, Parkhomenko E, Pato MT, Paunio T, Perkins DO, Pers TH, Pietiläinen O, Pimm J, Pocklington AJ, Powell J, Price A, Pulver AE, Purcell SM, Quested D, Rasmussen HB, Reichenberg A, Reimers MA, Richards AL, Roffman JL, Roussos P, Ruderfer DM, Salomaa V, Sanders AR, Savitz A, Schall U, Schulze TG, Schwab SG, Scolnick EM, Scott RJ, Seidman LJ, Shi J, Silverman JM, Smoller JW, Söderman E, Spencer CCA, Stahl EA, Strengman E, Strohmaier J, Stroup TS, Suvisaari J, Svrakic DM, Szatkiewicz JP, Thirumalai S, Tooney PA, Veijola J, Visscher PM, Waddington J, Walsh D, Webb BT, Weiser M, Wildenauer DB, Williams NM, Williams S, Witt SH, Wolen AR, Wormley BK, Wray NR, Wu JQ, Zai CC, Adolfsson R, Andreassen OA, Blackwood DHR, Bramon E, Buxbaum JD, Cichon S, Collier DA, Corvin A, Daly MJ, Darvasi A, Domenici E, Esko T, Gejman PV, Gill M, Gurling H, Hultman CM, Iwata N, Jablensky AV, Jönsson EG, Kendler KS, Kirov G, Knight J, Levinson DF, Li QS, McCarroll SA, McQuillin A, Moran JL, Mowry BJ, Nöthen MM, Ophoff RA, Owen MJ, Palotie A, Pato CN, Petryshen TL, Posthuma D, Rietschel M, Riley BP, Rujescu D, Sklar P, St Clair D, Walters JTR, Werge T, Sullivan PF, O'Donovan MC, Scherer SW, Neale BM, Sebat J, Psychosis Endophenotypes International Consortium, CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium. Contribution of copy number variants to schizophrenia from a genome-wide study of 41, 321 subjects. Nat Genet 2017;49:27-35.
Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker H, Hamid R, Hannig V, Abdel-Hamid H, Bader P, McCracken E, Niyazov D, Leppig K, Thiese H, Hummel M, Alexander N, Gorski J, Kussmann J, Shashi V, Johnson K, Rehder C, Ballif BC, Shaffer LG, Eichler EE. A copy number variation morbidity map of developmental delay. Nat Genet 2011;43:838-46.
de Kovel CGF, Trucks H, Helbig I, Mefford HC, Baker C, Leu C, Kluck C, Muhle H, von Spiczak S, Ostertag P, Obermeier T, Kleefuss-Lie AA, Hallmann K, Steffens M, Gaus V, Klein KM, Hamer HM, Rosenow F, Brilstra EH, Trenité DK-N, Swinkels MEM, Weber YG, Unterberger I, Zimprich F, Urak L, Feucht M, Fuchs K, Møller RS, Hjalgrim H, De Jonghe P, Suls A, Rückert I-M, Wichmann H-E, Franke A, Schreiber S, Nürnberg P, Elger CE, Lerche H, Stephani U, Koeleman BPC, Lindhout D, Eichler EE, Sander T. Recurrent microdeletions at 15q11. 2 and 16p13. 11 predispose to idiopathic generalized epilepsies. Brain 2010;133:23-32.
Ulfarsson MO, Walters GB, Gustafsson O, Steinberg S, Silva A, Doyle OM, Brammer M, Gudbjartsson DF, Arnarsdottir S, Jonsdottir GA, Gisladottir RS, Bjornsdottir G, Helgason H, Ellingsen LM, Halldorsson JG, Saemundsen E, Stefansdottir B, Jonsson L, Eiriksdottir VK, Eiriksdottir GR, Johannesdottir GH, Unnsteinsdottir U, Jonsdottir B, Magnusdottir BB, Sulem P, Thorsteinsdottir U, Sigurdsson E, Brandeis D, Meyer-Lindenberg A, Stefansson H, Stefansson K. 15q11. 2 CNV affects cognitive, structural and functional correlates of dyslexia and dyscalculia. Transl Psychiatry 2017;7:e1109.
G eng J, Picker J, Zheng Z, Zhang X, Wang J, Hisama F, Brown DW, Mullen MP, Harris D, Stoler J, Seman A, Miller DT, Fu Q, Roberts AE, Shen Y. Chromosome microarray testing for patients with congenital heart defects reveals novel disease causing loci and high diagnostic yield. BMC Genomics 2014;15.
G lessner JT, Bick AG, Ito K, Homsy J, Rodriguez-Murillo L, Fromer M, Mazaika E, Vardarajan B, Italia M, Leipzig J, DePalma SR, Golhar R, Sanders SJ, Yamrom B, Ronemus M, Iossifov I, Willsey AJ, State MW, Kaltman JR, White PS, Shen Y, Warburton D, Brueckner M, Seidman C, Goldmuntz E, Gelb BD, Lifton R, Seidman J, Hakonarson H, Chung WK. Increased frequency of de novo copy number variants in congenital heart disease by integrative analysis of single nucleotide polymorphism array and exome sequence data. Circ Res 2014;115:884-96.
Soemedi R, Wilson IJ, Bentham J, Darlay R, Töpf A, Zelenika D, Cosgrove C, Setchfield K, Thornborough C, Granados-Riveron J, Blue GM, Breckpot J, Hellens S, Zwolinkski S, Glen E, Mamasoula C, Rahman TJ, Hall D, Rauch A, Devriendt K, Gewillig M, O' Sullivan J, Winlaw DS, Bu'Lock F, Brook JD, Bhattacharya S, Lathrop M, Santibanez-Koref M, Cordell HJ, Goodship JA, Keavney BD. Contribution of global rare copynumber variants to the risk of sporadic congenital heart disease. Am J Hum Genet 2012;91:489-501.
Cox DM, Butler MG. The 15q11. 2 BP1-BP2 microdeletion syndrome: a review. Int J Mol Sci 2015;16:4068-82.
R osenfeld JA, Coe BP, Eichler EE, Cuckle H, Shaffer LG. Estimates of penetrance for recurrent pathogenic copy-number variations. Genet Med 2013;15:478-81.
Chai J-H, Locke DP, Greally JM, Knoll JHM, Ohta T, Dunai J, Yavor A, Eichler EE, Nicholls RD. Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons. Am J Hum Genet 2003;73:898-925.
De Rubeis S, Pasciuto E, Li KW, Fernández E, Di Marino D, Buzzi A, Ostroff LE, Klann E, Zwartkruis FJT, Komiyama NH, Grant SGN, Poujol C, Choquet D, Achsel T, Posthuma D, Smit AB, Bagni C. CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation. Neuron 2013;79:1169-82.
Oguro-Ando A, Rosensweig C, Herman E, Nishimura Y, Werling D, Bill BR, Berg JM, Gao F, Coppola G, Abrahams BS, Geschwind DH. Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR. Mol Psychiatry 2015;20:1069-78.
R ainier S, Chai J-H, Tokarz D, Nicholls RD, Fink JK. NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). Am J Hum Genet 2003;73:967-71.
De Wolf V, Brison N, Devriendt K, Peeters H. Genetic counseling for susceptibility loci and neurodevelopmental disorders: the del15q11. 2 as an example. Am J Med Genet A 2013;161A:2846-54.
Kendall KM, Rees E, Escott-Price V, Einon M, Thomas R, Hewitt J, O'Donovan MC, Owen MJ, Walters JTR, Kirov G. Cognitive performance among carriers of pathogenic copy number variants: analysis of 152, 000 UK Biobank subjects. Biol Psychiatry 2017;82:103-10.
Firth HV, Richards SM, Bevan AP, Clayton S, Corpas M, Rajan D, Van Vooren S, Moreau Y, Pettett RM, Carter NP. Decipher: database of chromosomal imbalance and phenotype in humans using Ensembl resources. Am J Hum Genet 2009;84:524-33.
Burnside RD, Pasion R, Mikhail FM, Carroll AJ, Robin NH, Youngs EL, Gadi IK, Keitges E, Jaswaney VL, Papenhausen PR, Potluri VR, Risheg H, Rush B, Smith JL, Schwartz S, Tepperberg JH, Butler MG. Microdeletion/microduplication of proximal 15q11. 2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay. Hum Genet 2011;130:517-28.
Cafferkey M, Ahn JW, Flinter F, Ogilvie C. Phenotypic features in patients with 15q11. 2(BP1-BP2) deletion: further delineation of an emerging syndrome. Am J Med Genet A 2014;164A:1916-22.
Chaste P, Sanders SJ, Mohan KN, Klei L, Song Y, Murtha MT, Hus V, Lowe JK, Willsey AJ, Moreno-De-Luca D, Yu TW, Fombonne E, Geschwind D, Grice DE, Ledbetter DH, Lord C, Mane SM, Martin DM, Morrow EM, Walsh CA, Sutcliffe JS, State MW, Martin CL, Devlin B, Beaudet AL, Cook EH, Kim S-J. Modest impact on risk for autism spectrum disorder of rare copy number variants at 15q11. 2, specifically breakpoints 1 to 2. Autism Res 2014;7:355-62.
Coe BP, Witherspoon K, Rosenfeld JA, van Bon BWM, Vulto-van Silfhout AT, Bosco P, Friend KL, Baker C, Buono S, Vissers LELM, Schuurs-Hoeijmakers JH, Hoischen A, Pfundt R, Krumm N, Carvill GL, Li D, Amaral D, Brown N, Lockhart PJ, Scheffer IE, Alberti A, Shaw M, Pettinato R, Tervo R, de Leeuw N, Reijnders MRF, Torchia BS, Peeters H, O'Roak BJ, Fichera M, Hehir-Kwa JY, Shendure J, Mefford HC, Haan E, Gécz J, de Vries BBA, Romano C, Eichler EE. Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nat Genet 2014;46:1063-71.
Doornbos M, Sikkema-Raddatz B, Ruijvenkamp CAL, Dijkhuizen T, Bijlsma EK, Gijsbers AC J, Hilhorst-Hofstee Y, Hordijk R, Verbruggen KT, Kerstjens-Frederikse WSM, van Essen T, Kok K, van Silfhout AT, Breuning M, van Ravenswaaij-Arts CMA. Nine patients with a microdeletion 15q11. 2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances. Eur J Med Genet 2009;52:108-15.
Jiang Y, Zhang Y, Zhang P, Sang T, Zhang F, Ji T, Huang Q, Xie H, Du R, Cai B, Zhao H, Wang J, Wu Y, Wu H, Xu K, Liu X, Chan P, Wu X. NIPA2 located in 15q11. 2 is mutated in patients with childhood absence epilepsy. Hum Genet 2012;131:1217-24.
Kirov G, Rees E, Walters JTR, Escott-Price V, Georgieva L, Richards AL, Chambert KD, Davies G, Legge SE, Moran JL, McCarroll SA, O'Donovan MC, Owen MJ. The penetrance of copy number variations for schizophrenia and developmental delay. Biol Psychiatry 2014;75:378-85.
Mefford HC, Eichler EE. Duplication hotspots, rare genomic disorders, and common disease. Curr Opin Genet Dev 2009;19:196-204.
Mefford HC, Muhle H, Ostertag P, von Spiczak S, Buysse K, Baker C, Franke A, Malafosse A, Genton P, Thomas P, Gurnett CA, Schreiber S, Bassuk AG, Guipponi M, Stephani U, Helbig I, Eichler EE. Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genet 2010;6:e1000962.
Mullen SA, Carvill GL, Bellows S, Bayly MA, Trucks H, Lal D, Sander T, Berkovic SF, Dibbens LM, Scheffer IE, Mefford HC. Copy number variants are frequent in genetic generalized epilepsy with intellectual disability. Neurology 2013;81:1507-14.
R udd DS, Axelsen M, Epping EA, Andreasen NC, Wassink TH. A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model. Am J Med Genet B Neuropsychiatr Genet 2014;165B:619-26.
Stefansson H, Rujescu D, Cichon S, Pietiläinen OPH, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Möller H-J, Hartmann A, Shianna KV, Ge D, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di Forti M, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Mühleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nöthen MM, Peltonen L, Collier DA, St Clair D, Stefansson K. Large recurrent microdeletions associated with schizophrenia. Nature 2008;455:232-6.
R einthaler EM, Lal D, Lebon S, Hildebrand MS, Dahl H-HM, Regan BM, Feucht M, Steinböck H, Neophytou B, Ronen GM, Roche L, Gruber-Sedlmayr U, Geldner J, Haberlandt E, Hoffmann P, Herms S, Gieger C, Waldenberger M, Franke A, Wittig M, Schoch S, Becker AJ, Hahn A, Männik K, Toliat MR, Winterer G, Lerche H, Nürnberg P, Mefford H, Scheffer IE, Berkovic SF, Beckmann JS, Sander T, Jacquemont S, Reymond A, Zimprich F, Neubauer BA, 16p11. 2 European Consortium, EPICURE Consortium, EuroEPINOMICS Consortium. 16p11. 2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy. Hum Mol Genet 2014;23:6069-80.
van der Zwaag B, Staal WG, Hochstenbach R, Poot M, Spierenburg HA, de Jonge MV, Verbeek NE, van 't Slot R, van Es MA, Staal FJ, Freitag CM, Buizer-Voskamp JE, Nelen MR, van den Berg LH, van Amstel HKP, van Engeland H, Burbach JPH. A co-segregating microduplication of chromosome 15q11. 2 pinpoints two risk genes for autism spectrum disorder. Am J Med Genet B Neuropsychiatr Genet 2010;153B:960-6.
A merican Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th edn. Washington, DC: American Psychiatric Publishing, 2013.
Huguet G, Schramm C, Douard E, Jiang L, Labbe A, Tihy F, Mathonnet G, Nizard S, Lemyre E, Mathieu A, Poline J-B, Loth E, Toro R, Schumann G, Conrod P, Pausova Z, Greenwood C, Paus T, Bourgeron T, Jacquemont S, Consortium I, IMAGEN Consortium. Measuring and estimating the effect sizes of copy number variants on general intelligence in community-based samples. JAMA Psychiatry 2018;75:447-57.
Department of Biostatistics VU. lrm function | R documentation. Available: https:// www. rdocumentation. org/ packages/ rms/ versions/ 5. 1-2/ topics/ lrm
Viechtbauer W. Conducting Meta-Analyses in R with the metafor Package. J Stat Software 2010;36:1-48.
L ek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won H-H, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG, Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60, 706 humans. Nature 2016;536:285-91.
G ottesman II, Shields J. A polygenic theory of schizophrenia. Proc Natl Acad Sci U S A 1967;58:199-205.
Kim H, Thurman DJ, Durgin T, Faught E, Helmers S. Estimating epilepsy incidence and prevalence in the US pediatric population using nationwide health insurance claims data. J Child Neurol 2016;31:743-9.
van der Linde D, Konings EEM, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJM, Roos-Hesselink JW. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 2011;58:2241-7.
Stefansson H, Meyer-Lindenberg A, Steinberg S, Magnusdottir B, Morgen K, Arnarsdottir S, Bjornsdottir G, Walters GB, Jonsdottir GA, Doyle OM, Tost H, Grimm O, Kristjansdottir S, Snorrason H, Davidsdottir SR, Gudmundsson LJ, Jonsson GF, Stefansdottir B, Helgadottir I, Haraldsson M, Jonsdottir B, Thygesen JH, Schwarz AJ, Didriksen M, Stensbøl TB, Brammer M, Kapur S, Halldorsson JG, Hreidarsson S, Saemundsen E, Sigurdsson E, Stefansson K. CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 2014;505:361-6.
Visscher PM, Hill WG, Wray NR. Heritability in the genomics era-concepts and misconceptions. Nat Rev Genet 2008;9:255-66.
A bekhoukh S, Sahin HB, Grossi M, Zongaro S, Maurin T, Madrigal I, Kazue-Sugioka D, Raas-Rothschild A, Doulazmi M, Carrera P, Stachon A, Scherer S, Drula Do Nascimento MR, Trembleau A, Arroyo I, Szatmari P, Smith IM, Milà M, Smith AC, Giangrande A, Caillé I, Bardoni B. New insights into the regulatory function of CYFIP1 in the context of WAVE-and FMRP-containing complexes. Dis Model Mech 2017;10:463-74.
Plomin R, Deary IJ. Genetics and intelligence differences: five special findings. Mol Psychiatry 2015;20:98-108.
Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST, Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of medical genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med 2011;13:680-5.
Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86:749-64.
L andrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J, Jang W, Katz K, Ovetsky M, Riley G, Sethi A, Tully R, Villamarin-Salomon R, Rubinstein W, Maglott DR. ClinVar: public archive of interpretations of clinically relevant variants. Nucl Acids Res 2016;44:D862-D868.