An Amish founder population reveals rare-population genetic determinants of the human lipidome.
An Amish founder population reveals rare-population genetic determinants of the human lipidome.
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DOI：
10.1038/s42003-022-03291-2
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发表时间：
2022-04-07
影响因子：
5.9
通讯作者：
O'Connell JR
中科院分区：
文献类型：
--
作者：
Montasser ME;Aslibekyan S;Srinivasasainagendra V;Tiwari HK;Patki A;Bagheri M;Kind T;Barupal DK;Fan S;Perry J;Ryan KA;Shuldiner AR;Arnett DK;Beitelshees AL;Irvin MR;O'Connell JR
确定脂质种类（脂质组）个体间变异的遗传决定因素，可以提供更深入的理解，并进一步了解复杂脂质组途径在CVD风险和进展中的机制作用，而不仅仅是简单的传统脂质。以前的研究主要是基于人群的，因此只能发现与常见遗传变异的联系。创始群体代表了一个强大的资源，可以加速发现以前未知的与罕见群体等位基因相关的生物学，这些等位基因由于遗传漂变而上升到更高的频率。我们对650名Amish创始人人群中的355种脂质进行了全基因组关联扫描，其中包括127种以前未测试过的脂质。据我们所知，我们首次报道了与两个罕见种群但富含阿米什的脂质变异相关的脂质物种：APOB_rs5742904和APOC3_rs76353203。我们还发现了3个罕见种群阿米什富位点与几种鞘脂的新关联，并提出了每个位点的潜在功能/因果变异，包括GLTPD2_rs536055318， CERS5_rs771033566和AKNA_rs531892793。我们复制了7个已知的常见位点，包括与两种甾醇的新关联：雄烯二醇与UGT位点，雌三醇与SLC22A8/A24位点。我们的研究结果显示了创始人群体和详细的脂质组在发现新的性状相关变异方面的双重力量。对旧阶Amish创始人群体355种脂质进行的GWAS分析揭示了Amish富集位点与几种鞘脂之间的关联。
Identifying the genetic determinants of inter-individual variation in lipid species (lipidome) may provide deeper understanding and additional insight into the mechanistic effect of complex lipidomic pathways in CVD risk and progression beyond simple traditional lipids. Previous studies have been largely population based and thus only powered to discover associations with common genetic variants. Founder populations represent a powerful resource to accelerate discovery of previously unknown biology associated with rare population alleles that have risen to higher frequency due to genetic drift. We performed a genome-wide association scan of 355 lipid species in 650 individuals from the Amish founder population including 127 lipid species not previously tested. To the best of our knowledge, we report for the first time the lipid species associated with two rare-population but Amish-enriched lipid variants: APOB_rs5742904 and APOC3_rs76353203. We also identified novel associations for 3 rare-population Amish-enriched loci with several sphingolipids and with proposed potential functional/causal variant in each locus including GLTPD2_rs536055318, CERS5_rs771033566, and AKNA_rs531892793. We replicated 7 previously known common loci including novel associations with two sterols: androstenediol with UGT locus and estriol with SLC22A8/A24 locus. Our results show the double power of founder populations and detailed lipidome to discover novel trait-associated variants. A GWAS of 355 lipid species in the Old Order Amish founder population reveals associations between Amish-enriched loci and several sphingolipids.
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影响因子：
4.5
作者：
Hicks AA;Pramstaller PP;Johansson A;Vitart V;Rudan I;Ugocsai P;Aulchenko Y;Franklin CS;Liebisch G;Erdmann J;Jonasson I;Zorkoltseva IV;Pattaro C;Hayward C;Isaacs A;Hengstenberg C;Campbell S;Gnewuch C;Janssens AC;Kirichenko AV;König IR;Marroni F;Polasek O;Demirkan A;Kolcic I;Schwienbacher C;Igl W;Biloglav Z;Witteman JC;Pichler I;Zaboli G;Axenovich TI;Peters A;Schreiber S;Wichmann HE;Schunkert H;Hastie N;Oostra BA;Wild SH;Meitinger T;Gyllensten U;van Duijn CM;Wilson JF;Wright A;Schmitz G;Campbell H
通讯作者：
Campbell H
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
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
全基因组关联荟萃分析产生了20个与胆结石疾病相关的基因座。
影响因子：
16.6
作者：
Ferkingstad E;Oddsson A;Gretarsdottir S;Benonisdottir S;Thorleifsson G;Deaton AM;Jonsson S;Stefansson OA;Norddahl GL;Zink F;Arnadottir GA;Gunnarsson B;Halldorsson GH;Helgadottir A;Jensson BO;Kristjansson RP;Sveinbjornsson G;Sverrisson DA;Masson G;Olafsson I;Eyjolfsson GI;Sigurdardottir O;Holm H;Jonsdottir I;Olafsson S;Steingrimsdottir T;Rafnar T;Bjornsson ES;Thorsteinsdottir U;Gudbjartsson DF;Sulem P;Stefansson K
通讯作者：
Stefansson K
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M