Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.
Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.
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NHLBI TOPMed计划中53，831个不同基因组的测序。
DOI：
10.1038/s41586-021-03205-y
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发表时间：
2021-03
期刊：
影响因子：
64.8
通讯作者：
Abecasis GR
中科院分区：
文献类型：
--
作者：
Taliun D;Harris DN;Kessler MD;Carlson J;Szpiech ZA;Torres R;Taliun SAG;Corvelo A;Gogarten SM;Kang HM;Pitsillides AN;LeFaive J;Lee SB;Tian X;Browning BL;Das S;Emde AK;Clarke WE;Loesch DP;Shetty AC;Blackwell TW;Smith AV;Wong Q;Liu X;Conomos MP;Bobo DM;Aguet F;Albert C;Alonso A;Ardlie KG;Arking DE;Aslibekyan S;Auer PL;Barnard J;Barr RG;Barwick L;Becker LC;Beer RL;Benjamin EJ;Bielak LF;Blangero J;Boehnke M;Bowden DW;Brody JA;Burchard EG;Cade BE;Casella JF;Chalazan B;Chasman DI;Chen YI;Cho MH;Choi SH;Chung MK;Clish CB;Correa A;Curran JE;Custer B;Darbar D;Daya M;de Andrade M;DeMeo DL;Dutcher SK;Ellinor PT;Emery LS;Eng C;Fatkin D;Fingerlin T;Forer L;Fornage M;Franceschini N;Fuchsberger C;Fullerton SM;Germer S;Gladwin MT;Gottlieb DJ;Guo X;Hall ME;He J;Heard-Costa NL;Heckbert SR;Irvin MR;Johnsen JM;Johnson AD;Kaplan R;Kardia SLR;Kelly T;Kelly S;Kenny EE;Kiel DP;Klemmer R;Konkle BA;Kooperberg C;Köttgen A;Lange LA;Lasky-Su J;Levy D;Lin X;Lin KH;Liu C;Loos RJF;Garman L;Gerszten R;Lubitz SA;Lunetta KL;Mak ACY;Manichaikul A;Manning AK;Mathias RA;McManus DD;McGarvey ST;Meigs JB;Meyers DA;Mikulla JL;Minear MA;Mitchell BD;Mohanty S;Montasser ME;Montgomery C;Morrison AC;Murabito JM;Natale A;Natarajan P;Nelson SC;North KE;O'Connell JR;Palmer ND;Pankratz N;Peloso GM;Peyser PA;Pleiness J;Post WS;Psaty BM;Rao DC;Redline S;Reiner AP;Roden D;Rotter JI;Ruczinski I;Sarnowski C;Schoenherr S;Schwartz DA;Seo JS;Seshadri S;Sheehan VA;Sheu WH;Shoemaker MB;Smith NL;Smith JA;Sotoodehnia N;Stilp AM;Tang W;Taylor KD;Telen M;Thornton TA;Tracy RP;Van Den Berg DJ;Vasan RS;Viaud-Martinez KA;Vrieze S;Weeks DE;Weir BS;Weiss ST;Weng LC;Willer CJ;Zhang Y;Zhao X;Arnett DK;Ashley-Koch AE;Barnes KC;Boerwinkle E;Gabriel S;Gibbs R;Rice KM;Rich SS;Silverman EK;Qasba P;Gan W;NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium;Papanicolaou GJ;Nickerson DA;Browning SR;Zody MC;Zöllner S;Wilson JG;Cupples LA;Laurie CC;Jaquish CE;Hernandez RD;O'Connor TD;Abecasis GR
TRANS-OMICS for Precision Medicine(TOPMed)计划旨在阐明心、肺、血液和睡眠障碍的遗传结构和生物学，最终目标是改进这些疾病的诊断、治疗和预防。该方案的最初阶段侧重于对具有丰富表型数据和不同背景的个人进行全基因组测序。在这里，我们描述TOPMed的目标和设计，以及可用的资源和从序列数据中获得的早期见解。这些资源包括一个变异浏览器、一个基因定位服务器，以及可通过DBGaP(基因类型和表型数据库)获得的基因组和表型数据。在第一批53,831个TOPMed样本中，我们检测到与参考基因组比对后超过4亿个单核苷酸和插入或缺失变体。通过组装未映射的读数和对高度可变的基因座进行定制分析，检测到了其他以前未描述的变体。在检测到的4亿多个变异中，97%的频率不到1%，46%是只在一个个体中存在的单身个体(53%在不相关的个体中)。这些罕见的变异提供了对突变过程和最近人类进化史的洞察。TOPMed研究中广泛的遗传变异目录为探索稀有和非编码序列变异对表型变异的贡献提供了独特的机会。此外，将TOPMed单倍型与现代补偿方法相结合，提高了全基因组关联研究的能力和覆盖范围，将变异的频率降至约0.01%。描述了NHLBI精密医学转基因计划(TOPMed)的目标、资源和设计，对第一批53,831个样本中检测到的罕见变异的分析提供了对突变过程和最近人类进化史的洞察。
The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes). In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%. The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.
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影响因子：
64.8
作者：
Bick AG;Weinstock JS;Nandakumar SK;Fulco CP;Bao EL;Zekavat SM;Szeto MD;Liao X;Leventhal MJ;Nasser J;Chang K;Laurie C;Burugula BB;Gibson CJ;Lin AE;Taub MA;Aguet F;Ardlie K;Mitchell BD;Barnes KC;Moscati A;Fornage M;Redline S;Psaty BM;Silverman EK;Weiss ST;Palmer ND;Vasan RS;Burchard EG;Kardia SLR;He J;Kaplan RC;Smith NL;Arnett DK;Schwartz DA;Correa A;de Andrade M;Guo X;Konkle BA;Custer B;Peralta JM;Gui H;Meyers DA;McGarvey ST;Chen IY;Shoemaker MB;Peyser PA;Broome JG;Gogarten SM;Wang FF;Wong Q;Montasser ME;Daya M;Kenny EE;North KE;Launer LJ;Cade BE;Bis JC;Cho MH;Lasky-Su J;Bowden DW;Cupples LA;Mak ACY;Becker LC;Smith JA;Kelly TN;Aslibekyan S;Heckbert SR;Tiwari HK;Yang IV;Heit JA;Lubitz SA;Johnsen JM;Curran JE;Wenzel SE;Weeks DE;Rao DC;Darbar D;Moon JY;Tracy RP;Buth EJ;Rafaels N;Loos RJF;Durda P;Liu Y;Hou L;Lee J;Kachroo P;Freedman BI;Levy D;Bielak LF;Hixson JE;Floyd JS;Whitsel EA;Ellinor PT;Irvin MR;Fingerlin TE;Raffield LM;Armasu SM;Wheeler MM;Sabino EC;Blangero J;Williams LK;Levy BD;Sheu WH;Roden DM;Boerwinkle E;Manson JE;Mathias RA;Desai P;Taylor KD;Johnson AD;NHLBI Trans-Omics for Precision Medicine Consortium;Auer PL;Kooperberg C;Laurie CC;Blackwell TW;Smith AV;Zhao H;Lange E;Lange L;Rich SS;Rotter JI;Wilson JG;Scheet P;Kitzman JO;Lander ES;Engreitz JM;Ebert BL;Reiner AP;Jaiswal S;Abecasis G;Sankaran VG;Kathiresan S;Natarajan P
通讯作者：
Natarajan P
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
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：
--
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
9.8
作者：
Browning, Sharon R.;Browning, Brian L.
通讯作者：
Browning, Brian L.