Citations 4
A large-scale multi-ethnic genome-wide association study of coronary artery disease
Tcheandjieu, Catherine , Zhu, Xiang , Clarke, Shoa L. , Lee, Kyung Min , Chen, Fei , Pyarajan, Saiju , Song, Rebecca J. , Plomondon, Mary E. , Waldo, Stephen W. , Sinnott-Armstrong, Nasa , Wojcik, Genevieve L. , Haessler, Jeffrey, Do, Ron , North, Kari, Haiman, Christopher, Bis, Joshua, Shen, Botong, Lange, Leslie A., Lu, Yingchang , Stanaway, Ian B. , Hebbring, Scott J. , Namjou, Bahram , Kaufman, Kenneth M. , Kamatani, Yoichiro, Ritchie, Marylyn D. , Baras, Aris , Natarajan, Pradeep , Raghavan, Sridharan , Lee, Jennifer , Tang, Hua, Sun, Yan V. , O’Donnell, Christopher J. , Kathiresan, Sekar , Saleheen, Danish , Gaziano, J. Michael , Reaven, Peter D. , Cho, Kelly , Graff, Mariaelisa , Huang, Jie , Clarke, Shoa L , Do, Ron , Natarajan, Pradeep , Min Lee, Kyung , Assimes, Themistocles L. , Hilliard, Austin T. , Napolioni, Valerio , Ma, Shining , Fang, Huaying , Gorman, Bryan R. , Maddox, Thomas M , Ho, Yuk-Lam Anne , Buyske, Steven , Kooperberg, Charles , Loos, Ruth J. F. , Verbanck, Marie , Chaudhary, Kumardeep , Avery, Christy L. , Marchand, Loı̈c Le , Wilkens, Lynne R. , Leonard, Hampton L. , Giri, Ayush , Dikilitas, Ozan , Kullo, Iftikhar J. , Jarvik, Gail P. , Gordon, Adam, Koyama, Satoshi , Ito, Kaoru , Ishigaki, Kazuyoshi , Kamatani, Yoichiro, Tsao, Noah L. , Verma, Shefali S. , Kember, Rachel L. , Lotta, Luca Andrea , Levin, Michael G. , Hauser, Elizabeth R. , Miller, Donald Ray , Vujković, Marijana , Huffman, Jennifer E. , Klarin, Derek , Voight, Benjamin F. , Rader, Daniel J , Chang, Kyong‐Mi , Damrauer, Scott M , Lynch, Julie A. , Wilson, Peter W.F. , Tsao, Philip S. , Bick, Alexander G.
No container title available | March 10, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Coronary artery disease (CAD) is a leading cause of death, yet its genetic determinants are not fully elucidated. We report a multi-ethnic genome-wide association study of CAD involving nearly a quarter of a million cases, incorporating the largest cohorts to date of Whites, Blacks, and Hispanics from the Million Veteran Program with existing studies including CARDIoGRAMplusC4D, UK Biobank, and Biobank Japan. We verify substantial and nearly equivalent heritability of CAD across multiple ancestral groups, discover 107 novel loci including the first nine on the X-chromosome, identify the first eight genome-wide significant loci among Blacks and Hispanics, and demonstrate that two common haplotypes are largely responsible for the risk stratification at the well-known 9p21 locus in most populations except those of African origin where both haplotypes are virtually absent. We identify 15 loci for angiographically derived burden of coronary atherosclerosis, which robustly overlap with the strongest and earliest loci reported to date for clinical CAD. Phenome-wide association analyses of novel loci and externally validated polygenic risk scores (PRS) augment signals from the insulin resistance cluster of risk factors and consequences, extend previously established pleiotropic associations of loci with traditional risk factors to include smoking and family history, and confirm a substantially reduced transferability of existing PRS to Blacks. Downstream integrative genomic analyses reinforce the critical role of endothelial, fibroblast, and smooth muscle cells within the coronary vessel wall in CAD susceptibility. Our study highlights the value of a multi-ethnic design in efficiently characterizing the genetic architecture of CAD across all human populations.
Detecting potential pleiotropy across cardiovascular and neurological diseases using univariate, bivariate, and multivariate methods on 43,870 individuals from the eMERGE network
Zhang, Xinyuan , Veturi, Yogasudha , Bone, William P. , Lucas, Anastasia, Hebbring, Scott J. , Stanaway, Ian B. , Jarvik, Gail P. , Crosslin, David R. , Larson, Eric B. , Sleiman, Patrick , Fasel, David , Wei, Wei‐Qi, Schaid, Daniel J. , Ritchie, Marylyn D. , Jarvik, Gail P , Wei, Wei-Qi , Verma, Shefali S. , Verma, Anurag , Denny, Joshua C. , Rasmussen‐Torvik, Laura J. , Pendergrass, Sarah A. , Smoller, Jordan W. , Håkonarson, Håkon , Weng, Chunhua , Kullo, Iftikhar J. , Chung, Wendy K.
Biocomputing 2019 | November 28, 2018 | Volume: No volume available | Issue: No issue available | Pages: 272-283
Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms
Hof, Femke N. G. van ’t, Ruigrok, Ynte M. , Lee, Cue Hyunkyu , Ripke, Stephan , Anderson, Graig, Baas, Annette F., Blankensteijn, Jan D. , Böttinger, Erwin P. , Bown, Matthew J. , Broderick, Joseph P., Bijlenga, Philippe , Crosslin, David R. , Ebeling, Christian , Eriksson, Johan G. , Fornage, Myriam , Foroud, Tatiana, Fraunberg, Mikael von und zu , Friedrich, Christoph M. , Gaál, Emília Ilona, Gottesman, Omri, Guo, Dongchuan , Harrison, Seamus C. , Hernesniemi, Juha , Hofman, Albert , Inoue, Ituro , Jääskeläinen, Juha E. , Kiemeney, Lambertus A. , Kivisaari, Riku , Ko, Nerissa , Koskinen, Seppo, Kubo, Michiaki , Kuivaniemi, Helena , Laakso, Aki , Lehto, Hanna, LeMaire, Scott A. , Malinowski, Jennifer , McCarty, Catherine A. , Mosley, Thomas H., Nakaoka, Hirofumi , Peissig, Peggy , Pera, Joanna , Rasmussen‐Torvik, Laura J. , Ritchie, Marylyn D. , Rivadeneira, Fernando , Rij, André M. van , Santos‐Cortez, Regie Lyn P., Saratzis, Athanasios , Słowik, Agnieszka , Tromp, Gerard , Uitterlinden, André G. , Vermeulen, Sita H. , Wang, Gao T., Han, Buhm , Bakker, Paul I. W. de , Verissimo, Ana Raquel, Wright, Benjamin J., Bumpstead, Suzannah, Grétarsdóttir, Sólveig , Badger, Stephen A., Child, Anne H. , Cockerill, Gillian, Hafez, Hany , Futers, Simon , Sohrabi, Soroush, Smith, Alberto, Thompson, Matthew M., Bockxmeer, Frank M. van, Matthíasson, Stefán E., Þorsteinsdóttir, Unnur , Graaf, Jacqueline de , Palmen, Jutta, Lindholt, Jes S. , Bradley, Declan , Waltham, Matthew, Gwilliam, Rhian, Golledge, Jonathan , Eriksson, Per , Stefánsson, Kāri , Thompson, John R., Humphries, Steve E. , Sayers, Robert D., Deloukas, Panos , Samani, Nilesh J. , Phillip, L. Victoria, Hill, Geraldine B., Williams, Michael , Thomson, Ian , Krysa, Jo, Wilkins, Gerard , Vasudevan, Thodor M., Lewis, David R. , Blair, Ross D., Hill, Andrew A., de Andrade, Mariza, Ripke, Stephan , Andrade, Mariza de , Broderick, Joseph, Carrell, David , Crawford, Dana C. , Jones, Gregory T. , Kullo, Iftikhar J. , Kurki, Mitja , Lai, Dongbing , Leal, Suzanne M. , Low, Siew‐Kee , Milewicz, Dianna M. , Nakamura, Yusuke , Niemela, Mika R. , Pacheco, Jennifer A. , Takahashi, Atsushi , Verma, Shefali S. , Rinkel, Gabriël J.E. , Clough, Rachel E. , Scott, D. Julian A., Þorleifsson, Guðmar , Teijink, Joep A.W. , Wijmenga, Cisca , Smith, Andrew J P , Edkins, Sarah , Hunt, Sarah E , Potter, Simon , Norman, Paul E , Powell, Janet T. , Merriman, Tony Raymond , Kiemeney, Lambertus A , Bijlenga, Philippe , Lindholt, Jes Sanddal , Malinowski, Jennnifer , Rasmussen-Torvik, Laura J , Eriksson, Per
Journal of the American Heart Association | July 15, 2016 | Volume: 5 | Issue: 7 | Pages: No page available
Background Intracranial aneurysms ( IAs ), abdominal aortic aneurysms ( AAAs ), and thoracic aortic aneurysms ( TAAs ) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs , AAAs, and TAAs . Methods and Results We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study ( GWAS ) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA , AAA , and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA ‐, AAA ‐, and TAA ‐associated SNP s and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls ( IA ) and 4391 cases and 37 904 controls ( AAA ), and found nominally significant associations for IA risk locus 18q11 near RBBP 8 to AAA (odds ratio [ OR ]=1.11; P =4.1×10 −5 ) and for TAA risk locus 15q21 near FBN 1 to AAA ( OR =1.07; P =1.1×10 −3 ). Conclusions Although there was no evidence for polygenic overlap between IAs , AAAs , and TAAs , we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs . These two loci will require further replication.
The phenotypic legacy of admixture between modern humans and Neandertals
Simonti, Corinne , Vernot, Benjamin , Bastarache, Lisa , Böttinger, Erwin P. , Chisholm, Rex L. , Crosslin, David R. , Hebbring, Scott J. , Jarvik, Gail P. , Li, Rongling, Pathak, Jyotishman , Ritchie, Marylyn D. , Roden, Dan M. , Tromp, Gerard , Prato, Jeffrey D., Bush, William S. , Akey, Joshua M. , Denny, Joshua C. , Capra, John A. , Carrell, David , Kullo, Iftikhar J. , Roden, Dan M. , Verma, Shefali S. , Denny, Joshua C , Jarvik, Gail P , Bush, William S
Science | February 12, 2016 | Volume: 351 | Issue: 6274 | Pages: 737-741
The legacy of human-Neandertal interbreeding Non-African humans are estimated to have inherited on average 1.5 to 4% of their genomes from Neandertals. However, how this genetic legacy affects human traits is unknown. Simonti et al. combined genotyping data with electronic health records. Individual Neandertal alleles were correlated with clinically relevant phenotypes in individuals of European descent. These archaic genetic variants were associated with medical conditions affecting the skin, the blood, and the risk of depression. Science , this issue p. 737