Gene-based association study for lipid traits in diverse cohorts implicates BACE1 and SIDT2 regulation in triglyceride levels.
Gene-based association study for lipid traits in diverse cohorts implicates BACE1 and SIDT2 regulation in triglyceride levels.
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作者：
Andaleon A;Mogil LS;Wheeler HE
血浆脂质水平是心血管疾病的危险因素，心血管疾病是全球死亡的主要原因。虽然已经进行了许多关于脂质遗传学的研究，但它们主要集中在欧洲人身上，因此它们对不同人群的可转移性尚不清楚。我们对来自尼日利亚和菲律宾的队列中的四种脂质性状进行了SNP和基因水平的全基因组关联研究（GWAS），并将其与更大的主要是欧洲荟萃分析的结果进行了比较。在我们的SNP水平GWAS中，尼日利亚队列中两个先前涉及的基因座在全基因组范围内具有显著性，即CETP中与HDL胆固醇相关的rs34065661（P = 9.0 × 10−10）和APOE上游与LDL胆固醇相关的rs 1065853（P = 6.6 × 10−9）。菲律宾队列中最高的SNP与甘油三酯水平相关（rs662799; P = 2.7 × 10−16），并且先前已在其他东亚研究中涉及。虽然这个SNP直接位于众所周知的APOA 5的上游，但我们发现它也可能参与BACE 1和SIDT 2的调节。我们的基于基因的关联分析PrediXcan显示，在几种组织中BACE 1表达降低和SIDT 2表达降低，均由rs662799驱动，与菲律宾人甘油三酯水平升高显著相关（FDR <0.1）。此外，我们的PrediXcan分析表明，基因调控是许多其他先前发现的脂质基因座相关性的基础机制。我们的新BACE 1和SIDT 2发现使用来自全球脂质遗传联盟（GLGC）Meta-GWAS的汇总统计数据进行了证实。
Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted on lipid genetics, they mainly focus on Europeans and thus their transferability to diverse populations is unclear. We performed SNP- and gene-level genome-wide association studies (GWAS) of four lipid traits in cohorts from Nigeria and the Philippines and compared them to the results of larger, predominantly European meta-analyses. Two previously implicated loci met genome-wide significance in our SNP-level GWAS in the Nigerian cohort, rs34065661 in CETP associated with HDL cholesterol (P = 9.0 × 10−10) and rs1065853 upstream of APOE associated with LDL cholesterol (P = 6.6 × 10−9). The top SNP in the Filipino cohort associated with triglyceride levels (rs662799; P = 2.7 × 10−16) and has been previously implicated in other East Asian studies. While this SNP is located directly upstream of well known APOA5, we show it may also be involved in the regulation of BACE1 and SIDT2. Our gene-based association analysis, PrediXcan, revealed decreased expression of BACE1 and decreased expression of SIDT2 in several tissues, all driven by rs662799, significantly associate with increased triglyceride levels in Filipinos (FDR <0.1). In addition, our PrediXcan analysis implicated gene regulation as the mechanism underlying the associations of many other previously discovered lipid loci. Our novel BACE1 and SIDT2 findings were confirmed using summary statistics from the Global Lipids Genetic Consortium (GLGC) meta-GWAS.
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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：
30.8
作者：
Loh, Po-Ru;Danecek, Petr;Palamara, Pier Francesco;Fuchsberger, Christian;Reshef, Yakir A.;Finucane, Hilary K.;Schoenherr, Sebastian;Forer, Lukas;McCarthy, Shane;Abecasis, Goncalo R.;Durbin, Richard;Price, Alkes L.
通讯作者：
Price, Alkes L.
影响因子：
4.6
作者：
Lin, Eugene;Kuo, Po-Hsiu;Tsai, Shih-Jen
通讯作者：
Tsai, Shih-Jen
影响因子：
5.8
作者：
Lee, S. H.;Yang, J.;Wray, N. R.
通讯作者：
Wray, N. R.