A large electronic-health-record-based genome-wide study of serum lipids.
A large electronic-health-record-based genome-wide study of serum lipids.
复制标题
DOI：
10.1038/s41588-018-0064-5
复制
发表时间：
2018-03
期刊：
影响因子：
30.8
通讯作者：
Risch N
中科院分区：
文献类型：
--
作者：
Hoffmann TJ;Theusch E;Haldar T;Ranatunga DK;Jorgenson E;Medina MW;Kvale MN;Kwok PY;Schaefer C;Krauss RM;Iribarren C;Risch N
一项针对94,674名多种族Kaiser Permanente成员的全基因组关联研究，利用478,866项纵向未经治疗的血脂电子健康记录衍生测量（EHRs），获得了多项新发现：121个新的SNP关联（46个主要关联，15个条件关联，60个来自全球脂质遗传联盟的荟萃分析）；方差增加33-42%可以用多次测量来解释；基因影响的性别差异（LDL、HDL、TC在女性中较大，TG则相反）；非西班牙裔白人、拉丁裔、非裔美国人和东亚人之间的差异；遗传显性和上位性，有强有力的证据表明，在ABOxFUT2上LDL均存在显性和上位性；和eQTL组织富集，涉及肝脏、脂肪和胰腺。利用电子病历药房数据，LDL和TG遗传风险评分（477个snp）都能强烈预测开始降脂治疗的年龄。这些发现强调了纵向电子病历在识别胆固醇和脂蛋白代谢的新遗传特征以及脂质治疗和冠心病风险方面的价值。
A genome-wide association study of 94,674 multi-ethnic Kaiser Permanente members utilizing 478,866 longitudinal untreated serum lipid electronic-health-record-derived measurements (EHRs) empowered multiple novel findings: 121 new SNP associations (46 primary, 15 conditional, 60 in meta-analysis with Global Lipids Genetic Consortium); increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater in females for LDL, HDL, TC, the opposite for TG); differences in variance explained amongst non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistasis, with strong evidence for both at ABOxFUT2 for LDL; and eQTL tissue-enrichment implicating the liver, adipose, and pancreas. Utilizing EHR pharmacy data, both LDL and TG genetic risk scores (477 SNPs) were strongly predictive of age-at-initiation of lipid-lowering treatment. These findings highlight the value of longitudinal EHRs for identifying novel genetic features of cholesterol and lipoprotein metabolism with implications for lipid treatment and risk of coronary heart disease.
登录
查看更多内容
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
3.7
作者：
Chen GB
通讯作者：
Chen GB
影响因子：
3.7
作者：
Elbers CC;Guo Y;Tragante V;van Iperen EP;Lanktree MB;Castillo BA;Chen F;Yanek LR;Wojczynski MK;Li YR;Ferwerda B;Ballantyne CM;Buxbaum SG;Chen YD;Chen WM;Cupples LA;Cushman M;Duan Y;Duggan D;Evans MK;Fernandes JK;Fornage M;Garcia M;Garvey WT;Glazer N;Gomez F;Harris TB;Halder I;Howard VJ;Keller MF;Kamboh MI;Kooperberg C;Kritchevsky SB;LaCroix A;Liu K;Liu Y;Musunuru K;Newman AB;Onland-Moret NC;Ordovas J;Peter I;Post W;Redline S;Reis SE;Saxena R;Schreiner PJ;Volcik KA;Wang X;Yusuf S;Zonderland AB;Anand SS;Becker DM;Psaty B;Rader DJ;Reiner AP;Rich SS;Rotter JI;Sale MM;Tsai MY;Borecki IB;Hegele RA;Kathiresan S;Nalls MA;Taylor HA Jr;Hakonarson H;Sivapalaratnam S;Asselbergs FW;Drenos F;Wilson JG;Keating BJ
通讯作者：
Keating BJ
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：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ