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AuthorGeorge, Hindy
AuthorDornbos, Peter
AuthorChaffin, Mark D.
AuthorLiu, Dajiang J.
AuthorWang, Minxian
AuthorSelvaraj, Margaret Sunitha
AuthorZhang, David
AuthorPark, Joseph
AuthorAguilar-Salinas, Carlos A.
AuthorAntonacci-Fulton, Lucinda
AuthorArdissino, Diego
AuthorArnett, Donna K.
AuthorAslibekyan, Stella
AuthorAtzmon, Gil
AuthorBallantyne, Christie M.
AuthorBarajas-Olmos, Francisco
AuthorBarzilai, Nir
AuthorBecker, Lewis C.
AuthorBielak, Lawrence F.
AuthorBis, Joshua C.
AuthorBlangero, John
AuthorBoerwinkle, Eric
AuthorBonnycastle, Lori L.
AuthorBottinger, Erwin
AuthorBowden, Donald W.
AuthorBown, Matthew J.
AuthorBrody, Jennifer A.
AuthorBroome, Jai G.
AuthorBurtt, Noël P.
AuthorCade, Brian E.
AuthorCenteno-Cruz, Federico
AuthorChan, Edmund
AuthorChang, Yi-Cheng
AuthorChen, Yii-Der I.
AuthorCheng, Ching-Yu
AuthorChoi, Won Jung
AuthorChowdhury, Rajiv
AuthorContreras-Cubas, Cecilia
AuthorCórdova, Emilio J.
AuthorCorrea, Adolfo
AuthorCupples, L. Adrienne
AuthorCurran, Joanne E.
AuthorDanesh, John
Authorde Vries, Paul S.
AuthorDeFronzo, Ralph A.
AuthorDoddapaneni, Harsha
AuthorDuggirala, Ravindranath
AuthorDutcher, Susan K.
AuthorEllinor, Patrick T.
AuthorEmery, Leslie S.
AuthorFlorez, Jose C.
AuthorFornage, Myriam
AuthorFreedman, Barry I.
AuthorFuster, Valentin
AuthorGaray-Sevilla, Ma. Eugenia
AuthorGarcía-Ortiz, Humberto
AuthorGermer, Soren
AuthorGibbs, Richard A.
AuthorGieger, Christian
AuthorGlaser, Benjamin
AuthorGonzalez, Clicerio
AuthorGonzalez-Villalpando, Maria Elena
AuthorGraff, Mariaelisa
AuthorGraham, Sarah E.
AuthorGrarup, Niels
AuthorGroop, Leif C.
AuthorGuo, Xiuqing
AuthorGupta, Namrata
AuthorHan, Sohee
AuthorHanis, Craig L.
AuthorHansen, Torben
AuthorHe, Jiang
AuthorHeard-Costa, Nancy L.
AuthorHung, Yi-Jen
AuthorHwang, Mi Yeong
AuthorIrvin, Marguerite R.
AuthorIslas-Andrade, Sergio
AuthorJarvik, Gail P.
AuthorKang, Hyun Min
AuthorKardia, Sharon L.R.
AuthorKelly, Tanika
AuthorKenny, Eimear E.
AuthorKhan, Alyna T.
AuthorKim, Bong-Jo
AuthorKim, Ryan W.
AuthorKim, Young Jin
AuthorKoistinen, Heikki A.
AuthorKooperberg, Charles
AuthorKuusisto, Johanna
AuthorKwak, Soo Heon
AuthorLaakso, Markku
AuthorLange, Leslie A.
AuthorLee, Jiwon
AuthorLee, Juyoung
AuthorLee, Seonwook
AuthorLehman, Donna M.
AuthorLemaitre, Rozenn N.
AuthorLinneberg, Allan
AuthorLiu, Jianjun
AuthorLoos, Ruth J.F.
AuthorLubitz, Steven A.
AuthorLyssenko, Valeriya
AuthorMa, Ronald C.W.
AuthorMartin, Lisa Warsinger
AuthorMartínez-Hernández, Angélica
AuthorMathias, Rasika A.
AuthorMcGarvey, Stephen T.
AuthorMcPherson, Ruth
AuthorMeigs, James B.
AuthorMeitinger, Thomas
AuthorMelander, Olle
AuthorMendoza-Caamal, Elvia
AuthorMetcalf, Ginger A.
AuthorMi, Xuenan
AuthorMohlke, Karen L.
AuthorMontasser, May E.
AuthorMoon, Jee-Young
AuthorMoreno-Macías, Hortensia
AuthorMorrison, Alanna C.
AuthorMuzny, Donna M.
AuthorNelson, Sarah C.
AuthorNilsson, Peter M.
AuthorO’Connell, Jeffrey R.
AuthorOrho-Melander, Marju
AuthorOrozco, Lorena
AuthorPalmer, Colin N.A.
AuthorPalmer, Nicholette D.
AuthorPark, Cheol Joo
AuthorPark, Kyong Soo
AuthorPedersen, Oluf
AuthorPeralta, Juan M.
AuthorPeyser, Patricia A.
AuthorPost, Wendy S.
AuthorPreuss, Michael
AuthorPsaty, Bruce M.
AuthorQi, Qibin
AuthorRao, D.C.
AuthorRedline, Susan
AuthorReiner, Alexander P.
AuthorRevilla-Monsalve, Cristina
AuthorRich, Stephen S.
AuthorSamani, Nilesh
AuthorSchunkert, Heribert
AuthorSchurmann, Claudia
AuthorSeo, Daekwan
AuthorSeo, Jeong-Sun
AuthorSim, Xueling
AuthorSladek, Rob
AuthorSmall, Kerrin S.
AuthorSo, Wing Yee
AuthorStilp, Adrienne M.
AuthorTai, E. Shyong
AuthorTam, Claudia H.T.
AuthorTaylor, Kent D.
AuthorTeo, Yik Ying
AuthorThameem, Farook
AuthorTomlinson, Brian
AuthorTsai, Michael Y.
AuthorTuomi, Tiinamaija
AuthorTuomilehto, Jaakko
AuthorTusié-Luna, Teresa
AuthorUdler, Miriam S.
Authorvan Dam, Rob M.
AuthorVasan, Ramachandran S.
AuthorViaud Martinez, Karine A.
AuthorWang, Fei Fei
AuthorWang, Xuzhi
AuthorWatkins, Hugh
AuthorWeeks, Daniel E.
AuthorWilson, James G.
AuthorWitte, Daniel R.
AuthorWong, Tien-Yin
AuthorYanek, Lisa R.
AuthorKathiresan, Sekar
AuthorRader, Daniel J.
AuthorRotter, Jerome I.
AuthorBoehnke, Michael
AuthorMcCarthy, Mark I.
AuthorWiller, Cristen J.
AuthorNatarajan, Pradeep
AuthorFlannick, Jason A.
AuthorKhera, Amit V.
AuthorPeloso, Gina M.
Available date2023-03-20T06:44:13Z
Publication Date2022-01-06
Publication NameThe American Journal of Human Genetics
Identifierhttp://dx.doi.org/10.1016/j.ajhg.2021.11.021
CitationHindy, G., Dornbos, P., Chaffin, M. D., Liu, D. J., Wang, M., Selvaraj, M. S., ... & So, W. Y. (2022). Rare coding variants in 35 genes associate with circulating lipid levels—a multi-ancestry analysis of 170,000 exomes. The American Journal of Human Genetics, 109(1), 81-96.
ISSN0002-9297
URIhttps://www.sciencedirect.com/science/article/pii/S0002929721004523
URIhttp://hdl.handle.net/10576/41173
AbstractLarge-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, SH2B3, and PLIN1) had no prior association of rare coding variants with lipid levels. Most of our associated genes showed evidence of association among multiple ancestries. Finally, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes and for genes closest to GWAS index single-nucleotide polymorphisms (SNPs). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels.
Languageen
PublisherElsevier
Subjectexome sequencing
association
lipid
cholesterol
gene-based association
TitleRare coding variants in 35 genes associate with circulating lipid levels—A multi-ancestry analysis of 170,000 exomes
TypeArticle
Pagination81-96
Issue Number1
Volume Number109
Open Access user License http://www.elsevier.com/open-access/userlicense/1.0/
ESSN1537-6605
dc.accessType Open Access


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