Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries
© 2018 The Author(s). Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole gen...
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/133991.2 |
| _version_ | 1811073131217944576 |
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| author | Kellis, Manolis |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Kellis, Manolis |
| author_sort | Kellis, Manolis |
| collection | MIT |
| description | © 2018 The Author(s). Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans. |
| first_indexed | 2024-09-23T09:28:36Z |
| format | Article |
| id | mit-1721.1/133991.2 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:28:36Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/133991.22022-09-30T17:25:04Z Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries Kellis, Manolis Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science © 2018 The Author(s). Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans. 2022-09-30T17:25:03Z 2021-10-27T19:57:32Z 2022-09-30T17:25:03Z 2018 2019-06-07T14:21:28Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133991.2 en 10.1038/S41467-018-04668-W Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/octet-stream Springer Science and Business Media LLC Nature |
| spellingShingle | Kellis, Manolis Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries |
| title | Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries |
| title_full | Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries |
| title_fullStr | Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries |
| title_full_unstemmed | Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries |
| title_short | Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries |
| title_sort | deep coverage whole genome sequences and plasma lipoprotein a in individuals of european and african ancestries |
| url | https://hdl.handle.net/1721.1/133991.2 |
| work_keys_str_mv | AT kellismanolis deepcoveragewholegenomesequencesandplasmalipoproteinainindividualsofeuropeanandafricanancestries |