eprintid: 1543936 rev_number: 47 eprint_status: archive userid: 608 dir: disk0/01/54/39/36 datestamp: 2017-03-05 05:01:22 lastmod: 2021-12-01 23:33:00 status_changed: 2017-03-16 09:58:38 type: article metadata_visibility: show creators_name: Shahid, SU creators_name: Shabana, . creators_name: Cooper, JA creators_name: Beaney, KE creators_name: Li, K creators_name: Rehman, A creators_name: Humphries, SE title: Genetic risk analysis of coronary artery disease in Pakistani subjects using a genetic risk score of 21 variants ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: D14 keywords: Conventional risk factors, Coronary artery disease, Genetic risk score note: © 2017 Elsevier B.V. All rights reserved. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at https://creativecommons.org/licenses/. Access may be initially restricted by the publisher. abstract: BACKGROUND AND AIMS: Conventional coronary artery disease (CAD) risk factors like age, gender, blood lipids, hypertension and smoking have been the basis of CAD risk prediction algorithms, but provide only modest discrimination. Genetic risk score (GRS) may provide improved discrimination over and above conventional risk factors. Here we analyzed the genetic risk of CAD in subjects from Pakistan, using a GRS of 21 variants in 18 genes and examined whether the GRS is associated with blood lipid levels. METHODS: 625 (405 cases and 220 controls) subjects were genotyped for variants, NOS3 rs1799983, SMAD3 rs17228212, APOB rs1042031, LPA rs3798220, LPA rs10455872, SORT1 rs646776, APOE rs429358, GLUL rs10911021, FTO rs9939609, MIA3 rs17465637, CDKN2Ars10757274, DAB2IP rs7025486, CXCL12 rs1746048, ACE rs4341, APOA5 rs662799, CETP rs708272, MRAS rs9818870, LPL rs328, LPL rs1801177, PCSK9 rs11591147 and APOE rs7412 by TaqMan and KASPar allele discrimination techniques. RESULTS: Individually, the single SNPs were not associated with CAD except APOB rs1042031 and FTO rs993969 (p = 0.01 and 0.009 respectively). However, the combined GRS of 21 SNPs was significantly higher in cases than controls (19.37 ± 2.56 vs. 18.47 ± 2.45, p = 2.9 × 10(-5)), and compared to the bottom quintile, CAD risk in the top quintile of the GRS was 2.96 (95% CI 1.71-5.13). Atherogenic blood lipids showed significant positive association with GRS. CONCLUSIONS: The GRS was quantitatively associated with CAD risk and showed association with blood lipid levels, suggesting that the mechanism of these variants is likely to be, in part at least, through creating an atherogenic lipid profile in subjects carrying high numbers of risk alleles. date: 2017-03 date_type: published official_url: http://doi.org/10.1016/j.atherosclerosis.2017.01.024 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1208734 doi: 10.1016/j.atherosclerosis.2017.01.024 pii: S0021-9150(17)30026-6 lyricists_name: Beaney, Katherine lyricists_name: Cooper, Jacqueline lyricists_name: Humphries, Stephen lyricists_id: BEANE45 lyricists_id: JCOOP43 lyricists_id: SEHUM16 actors_name: Humphries, Stephen actors_name: Laslett, David actors_id: SEHUM16 actors_id: DLASL34 actors_role: owner actors_role: impersonator full_text_status: public publication: Atherosclerosis volume: 258 pagerange: 1-7 event_location: Ireland issn: 1879-1484 citation: Shahid, SU; Shabana, .; Cooper, JA; Beaney, KE; Li, K; Rehman, A; Humphries, SE; (2017) Genetic risk analysis of coronary artery disease in Pakistani subjects using a genetic risk score of 21 variants. Atherosclerosis , 258 pp. 1-7. 10.1016/j.atherosclerosis.2017.01.024 <https://doi.org/10.1016/j.atherosclerosis.2017.01.024>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1543936/1/Humphries_Genetic%20risk%20score%20ath%20R2.pdf