Novel loci discovery for blood pressure and heart rate using the Exome chip
<p><b>Introduction:</b> Genome-wide association studies for many cardiovascular traits have primarily identified common variants with small effects, explaining only a small percentage of the total trait variance. The missing heritability may in part be explained by rare variants.&...
| Glavni autori: | , , , , , , , , , , |
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| Format: | Journal article |
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Nature Publishing Group
2016
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| _version_ | 1826291557457723392 |
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| author | Warren, H Surendran, P Manning, A van den Berg, M van der Harst, P Verweij, N Eijgelsheim, M Stricker, B Lindgren, C Howson, J Munroe, P |
| author_facet | Warren, H Surendran, P Manning, A van den Berg, M van der Harst, P Verweij, N Eijgelsheim, M Stricker, B Lindgren, C Howson, J Munroe, P |
| author_sort | Warren, H |
| collection | OXFORD |
| description | <p><b>Introduction:</b> Genome-wide association studies for many cardiovascular traits have primarily identified common variants with small effects, explaining only a small percentage of the total trait variance. The missing heritability may in part be explained by rare variants.</p> <p><b>Methods:</b> The Exome chip includes ~250,000 rare, low-frequency and common variants, thus enables the investigation of rare variant associations.</p> <p>Within large international consortia, we have led Exome chip analyses for blood pressure (BP) and heart rate (HR) in a total of ~350,000 and ~240,000 individuals, respectively.</p> <p><b>Results:</b> We identified 31 novel genetic regions associated with BP or hypertension, including rare missense variants in <i>RMB47</i>, <i>COL21A1</i> and <i>RRAS</i> with larger effects on BP than reported common variants, and <i>A2ML1</i>, a gene containing multiple rare variant associations.</p> <p>A novel low-frequency nonsense variant was identified in ENPEP, which encodes the APA enzyme of the renin-angiotensin-aldosterone system. ENPEP is a therapeutic target, and an ENPEP inhibitor is currently being tested in Phase IIa clinical trials for hypertension.</p> <p>For HR we identified nine novel loci, and new independent associations at some of the 21 published loci.</p> <p><b>Conclusions:</b> We have discovered 40 new loci for BP or HR. Of potential interest is an overlap between genetic associations for BP and HR.</p> <p>An association at MYH6, a new BP locus, is a published association for HR. RNF207 is a novel locus for both BP and HR, and is a published association for QT interval.</p> <p>This suggests there may be some similarities in underlying biological mechanisms, and may inform therapeutic strategies.</p> |
| first_indexed | 2024-03-07T03:01:11Z |
| format | Journal article |
| id | oxford-uuid:b104b9d0-09de-4c71-b79e-b0fd1a2c92a9 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T03:01:11Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:b104b9d0-09de-4c71-b79e-b0fd1a2c92a92022-03-27T04:00:48ZNovel loci discovery for blood pressure and heart rate using the Exome chipJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b104b9d0-09de-4c71-b79e-b0fd1a2c92a9Symplectic Elements at OxfordNature Publishing Group2016Warren, HSurendran, PManning, Avan den Berg, Mvan der Harst, PVerweij, NEijgelsheim, MStricker, BLindgren, CHowson, JMunroe, P <p><b>Introduction:</b> Genome-wide association studies for many cardiovascular traits have primarily identified common variants with small effects, explaining only a small percentage of the total trait variance. The missing heritability may in part be explained by rare variants.</p> <p><b>Methods:</b> The Exome chip includes ~250,000 rare, low-frequency and common variants, thus enables the investigation of rare variant associations.</p> <p>Within large international consortia, we have led Exome chip analyses for blood pressure (BP) and heart rate (HR) in a total of ~350,000 and ~240,000 individuals, respectively.</p> <p><b>Results:</b> We identified 31 novel genetic regions associated with BP or hypertension, including rare missense variants in <i>RMB47</i>, <i>COL21A1</i> and <i>RRAS</i> with larger effects on BP than reported common variants, and <i>A2ML1</i>, a gene containing multiple rare variant associations.</p> <p>A novel low-frequency nonsense variant was identified in ENPEP, which encodes the APA enzyme of the renin-angiotensin-aldosterone system. ENPEP is a therapeutic target, and an ENPEP inhibitor is currently being tested in Phase IIa clinical trials for hypertension.</p> <p>For HR we identified nine novel loci, and new independent associations at some of the 21 published loci.</p> <p><b>Conclusions:</b> We have discovered 40 new loci for BP or HR. Of potential interest is an overlap between genetic associations for BP and HR.</p> <p>An association at MYH6, a new BP locus, is a published association for HR. RNF207 is a novel locus for both BP and HR, and is a published association for QT interval.</p> <p>This suggests there may be some similarities in underlying biological mechanisms, and may inform therapeutic strategies.</p> |
| spellingShingle | Warren, H Surendran, P Manning, A van den Berg, M van der Harst, P Verweij, N Eijgelsheim, M Stricker, B Lindgren, C Howson, J Munroe, P Novel loci discovery for blood pressure and heart rate using the Exome chip |
| title | Novel loci discovery for blood pressure and heart rate using the Exome chip |
| title_full | Novel loci discovery for blood pressure and heart rate using the Exome chip |
| title_fullStr | Novel loci discovery for blood pressure and heart rate using the Exome chip |
| title_full_unstemmed | Novel loci discovery for blood pressure and heart rate using the Exome chip |
| title_short | Novel loci discovery for blood pressure and heart rate using the Exome chip |
| title_sort | novel loci discovery for blood pressure and heart rate using the exome chip |
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