Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.
Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.
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DOI：
10.1038/ng.3622
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发表时间：
2016-09
期刊：
影响因子：
30.8
通讯作者：
Veldink JH
中科院分区：
文献类型：
--
作者：
van Rheenen W;Shatunov A;Dekker AM;McLaughlin RL;Diekstra FP;Pulit SL;van der Spek RA;Võsa U;de Jong S;Robinson MR;Yang J;Fogh I;van Doormaal PT;Tazelaar GH;Koppers M;Blokhuis AM;Sproviero W;Jones AR;Kenna KP;van Eijk KR;Harschnitz O;Schellevis RD;Brands WJ;Medic J;Menelaou A;Vajda A;Ticozzi N;Lin K;Rogelj B;Vrabec K;Ravnik-Glavač M;Koritnik B;Zidar J;Leonardis L;Grošelj LD;Millecamps S;Salachas F;Meininger V;de Carvalho M;Pinto S;Mora JS;Rojas-García R;Polak M;Chandran S;Colville S;Swingler R;Morrison KE;Shaw PJ;Hardy J;Orrell RW;Pittman A;Sidle K;Fratta P;Malaspina A;Topp S;Petri S;Abdulla S;Drepper C;Sendtner M;Meyer T;Ophoff RA;Staats KA;Wiedau-Pazos M;Lomen-Hoerth C;Van Deerlin VM;Trojanowski JQ;Elman L;McCluskey L;Basak AN;Tunca C;Hamzeiy H;Parman Y;Meitinger T;Lichtner P;Radivojkov-Blagojevic M;Andres CR;Maurel C;Bensimon G;Landwehrmeyer B;Brice A;Payan CA;Saker-Delye S;Dürr A;Wood NW;Tittmann L;Lieb W;Franke A;Rietschel M;Cichon S;Nöthen MM;Amouyel P;Tzourio C;Dartigues JF;Uitterlinden AG;Rivadeneira F;Estrada K;Hofman A;Curtis C;Blauw HM;van der Kooi AJ;de Visser M;Goris A;Weber M;Shaw CE;Smith BN;Pansarasa O;Cereda C;Del Bo R;Comi GP;D'Alfonso S;Bertolin C;Sorarù G;Mazzini L;Pensato V;Gellera C;Tiloca C;Ratti A;Calvo A;Moglia C;Brunetti M;Arcuti S;Capozzo R;Zecca C;Lunetta C;Penco S;Riva N;Padovani A;Filosto M;Muller B;Stuit RJ;PARALS Registry;SLALOM Group;SLAP Registry;FALS Sequencing Consortium;SLAGEN Consortium;NNIPPS Study Group;Blair I;Zhang K;McCann EP;Fifita JA;Nicholson GA;Rowe DB;Pamphlett R;Kiernan MC;Grosskreutz J;Witte OW;Ringer T;Prell T;Stubendorff B;Kurth I;Hübner CA;Leigh PN;Casale F;Chio A;Beghi E;Pupillo E;Tortelli R;Logroscino G;Powell J;Ludolph AC;Weishaupt JH;Robberecht W;Van Damme P;Franke L;Pers TH;Brown RH;Glass JD;Landers JE;Hardiman O;Andersen PM;Corcia P;Vourc'h P;Silani V;Wray NR;Visscher PM;de Bakker PI;van Es MA;Pasterkamp RJ;Lewis CM;Breen G;Al-Chalabi A;van den Berg LH;Veldink JH
To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1–10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1126/science.aaa3650
发表时间：
2015-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cirulli ET;Lasseigne BN;Petrovski S;Sapp PC;Dion PA;Leblond CS;Couthouis J;Lu YF;Wang Q;Krueger BJ;Ren Z;Keebler J;Han Y;Levy SE;Boone BE;Wimbish JR;Waite LL;Jones AL;Carulli JP;Day-Williams AG;Staropoli JF;Xin WW;Chesi A;Raphael AR;McKenna-Yasek D;Cady J;Vianney de Jong JM;Kenna KP;Smith BN;Topp S;Miller J;Gkazi A;FALS Sequencing Consortium;Al-Chalabi A;van den Berg LH;Veldink J;Silani V;Ticozzi N;Shaw CE;Baloh RH;Appel S;Simpson E;Lagier-Tourenne C;Pulst SM;Gibson S;Trojanowski JQ;Elman L;McCluskey L;Grossman M;Shneider NA;Chung WK;Ravits JM;Glass JD;Sims KB;Van Deerlin VM;Maniatis T;Hayes SD;Ordureau A;Swarup S;Landers J;Baas F;Allen AS;Bedlack RS;Harper JW;Gitler AD;Rouleau GA;Brown R;Harms MB;Cooper GM;Harris T;Myers RM;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
48
作者：
Laaksovirta, Hannu;Peuralinna, Terhi;Schymick, Jennifer C.;Scholz, Sonja W.;Lai, Shaoi-Lin;Myllykangas, Liisa;Sulkava, Raimo;Jansson, Lilja;Hernandez, Dena G.;Gibbs, J. Raphael;Nalls, Michael A.;Heckerman, David;Tienari, Pentti J.;Traynor, Bryan J.
通讯作者：
Traynor, Bryan J.
影响因子：
30.8
作者：
Francioli, Laurent C.;Menelaou, Andronild;Wijmenga, Cisca
通讯作者：
Wijmenga, Cisca