Title | Rare coding variants in RCN3 are associated with blood pressure. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | He, KY, Kelly, TN, Wang, H, Liang, J, Zhu, L, Cade, BE, Assimes, TL, Becker, LC, Beitelshees, AL, Bielak, LF, Bress, AP, Brody, JA, Chang, Y-PChristy, Chang, Y-C, de Vries, PS, Duggirala, R, Fox, ER, Franceschini, N, Furniss, AL, Gao, Y, Guo, X, Haessler, J, Hung, Y-J, Hwang, S-J, Irvin, MRyan, Kalyani, RR, Liu, C-T, Liu, C, Martin, LWarsinger, Montasser, ME, Muntner, PM, Mwasongwe, S, Naseri, T, Palmas, W, Reupena, M'aSefuiva, Rice, KM, Sheu, WH-H, Shimbo, D, Smith, JA, Snively, BM, Yanek, LR, Zhao, W, Blangero, J, Boerwinkle, E, Chen, Y-DIda, Correa, A, L Cupples, A, Curran, JE, Fornage, M, He, J, Hou, L, Kaplan, RC, Kardia, SLR, Kenny, EE, Kooperberg, C, Lloyd-Jones, D, Loos, RJF, Mathias, RA, McGarvey, ST, Mitchell, BD, North, KE, Peyser, PA, Psaty, BM, Raffield, LM, Rao, DC, Redline, S, Reiner, AP, Rich, SS, Rotter, JI, Taylor, KD, Tracy, R, Vasan, RS, Morrison, AC, Levy, D, Chakravarti, A, Arnett, DK, Zhu, X |
Corporate Authors | Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium |
Journal | BMC Genomics |
Volume | 23 |
Issue | 1 |
Pagination | 148 |
Date Published | 2022 Feb 19 |
ISSN | 1471-2164 |
Keywords | Blood Pressure, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Precision Medicine, Whole Genome Sequencing |
Abstract | BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. RESULTS: Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10). CONCLUSIONS: Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits. |
DOI | 10.1186/s12864-022-08356-4 |
Alternate Journal | BMC Genomics |
PubMed ID | 35183128 |
PubMed Central ID | PMC8858539 |
Grant List | U01 HL054472 / HL / NHLBI NIH HHS / United States 75N95020D00003 / DA / NIDA NIH HHS / United States R01 HL071025 / HL / NHLBI NIH HHS / United States UL1 RR033176 / RR / NCRR NIH HHS / United States R01 HL112064 / HL / NHLBI NIH HHS / United States HHSN268201100037C / HL / NHLBI NIH HHS / United States U01 HG007417 / HG / NHGRI NIH HHS / United States 75N94020D00007 / HD / NICHD NIH HHS / United States HHSN268201500003C / HL / NHLBI NIH HHS / United States R01 HL113323 / HL / NHLBI NIH HHS / United States HHSN268201300005C / HL / NHLBI NIH HHS / United States K01 HL133468 / HL / NHLBI NIH HHS / United States 75N90020D00002 / CL / CLC NIH HHS / United States HHSN268201800012C / HL / NHLBI NIH HHS / United States HHSN268201300004C / HL / NHLBI NIH HHS / United States N01HC95160 / HL / NHLBI NIH HHS / United States R01 HL071251 / HL / NHLBI NIH HHS / United States R01 HL133040 / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States R01 HL087698 / HL / NHLBI NIH HHS / United States R01 HL046380 / HL / NHLBI NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States 75N92022D00007 / HL / NHLBI NIH HHS / United States R01 HL121007 / HL / NHLBI NIH HHS / United States HHSN268201600002C / HL / NHLBI NIH HHS / United States R01 HL131136 / HL / NHLBI NIH HHS / United States U01 DK085524 / DK / NIDDK NIH HHS / United States R01 HL111249 / HL / NHLBI NIH HHS / United States HHSN268201300001C / HL / NHLBI NIH HHS / United States R01 HL071259 / HL / NHLBI NIH HHS / United States HHSN268201600032C / ES / NIEHS NIH HHS / United States U01 HL054527 / HL / NHLBI NIH HHS / United States HHSN268201800004I / HL / NHLBI NIH HHS / United States N01HC95163 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States 75N96020D00002 / ES / NIEHS NIH HHS / United States HHSN268201600018C / HL / NHLBI NIH HHS / United States 75N94020D00003 / HD / NICHD NIH HHS / United States R01 HL092577 / HL / NHLBI NIH HHS / United States R21 HL140385 / HL / NHLBI NIH HHS / United States 75N93020D00002 / AI / NIAID NIH HHS / United States HHSN268201700004C / HB / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 HL087660 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States U01 HL054509 / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States U01 HL120393 / HL / NHLBI NIH HHS / United States 75N99020D00003 / OF / ORFDO NIH HHS / United States R01 HL113338 / HL / NHLBI NIH HHS / United States R01 DK117445 / DK / NIDDK NIH HHS / United States R01 HL153805 / HL / NHLBI NIH HHS / United States 75N95020D00002 / DA / NIDA NIH HHS / United States R01 HL071250 / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States N01HC65236 / HL / NHLBI NIH HHS / United States R01 DK110113 / DK / NIDDK NIH HHS / United States N01HC65235 / HL / NHLBI NIH HHS / United States R01 DK107786 / DK / NIDDK NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States HHSN268201800014C / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC65234 / HL / NHLBI NIH HHS / United States N02HL64278 / HL / NHLBI NIH HHS / United States R01 MH078111 / MH / NIMH NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States U01 HL054464 / HL / NHLBI NIH HHS / United States R01 HL119443 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States 75N90020D00003 / CL / CLC NIH HHS / United States 75N96020D00003 / ES / NIEHS NIH HHS / United States HHSN268201800003I / HL / NHLBI NIH HHS / United States R01 HG011052 / HG / NHGRI NIH HHS / United States R35 HL135818 / HL / NHLBI NIH HHS / United States R01 HL098433 / HL / NHLBI NIH HHS / United States 75N99020D00002 / OF / ORFDO NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 HL071051 / HL / NHLBI NIH HHS / United States N01HC65233 / HL / NHLBI NIH HHS / United States HHSN268201800007I / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States HHSN268201700001I / HL / NHLBI NIH HHS / United States HHSN268201800013I / MD / NIMHD NIH HHS / United States 75N99020D00006 / OF / ORFDO NIH HHS / United States HHSN268201500015C / HL / NHLBI NIH HHS / United States HHSN268201600003C / HL / NHLBI NIH HHS / United States U01 HL054457 / HL / NHLBI NIH HHS / United States HHSN268201600033C / ES / NIEHS NIH HHS / United States HHSN268201700004I / HL / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC65237 / HL / NHLBI NIH HHS / United States HHSN268201500016C / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States R56 HG010297 / HG / NHGRI NIH HHS / United States M01 RR000052 / RR / NCRR NIH HHS / United States 75N95020D00007 / DA / NIDA NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States UL1 TR001420 / TR / NCATS NIH HHS / United States R01 HL049762 / HL / NHLBI NIH HHS / United States U01 HL054498 / HL / NHLBI NIH HHS / United States 75N95020D00005 / DA / NIDA NIH HHS / United States HHSN268201600004C / HL / NHLBI NIH HHS / United States U01 HL072515 / HL / NHLBI NIH HHS / United States P01 HL045522 / HL / NHLBI NIH HHS / United States HHSN268201800011C / HL / NHLBI NIH HHS / United States U01 HL072518 / HL / NHLBI NIH HHS / United States P20 GM109036 / GM / NIGMS NIH HHS / United States HG003054 / HG / NHGRI NIH HHS / United States HHSN268201300003C / HG / NHGRI NIH HHS / United States HHSN268201500014C / HL / NHLBI NIH HHS / United States HHSN268201500003I / HL / NHLBI NIH HHS / United States KL2 TR002490 / TR / NCATS NIH HHS / United States HHSN268201600001C / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States HL086694 / HL / NHLBI NIH HHS / United States HHSN268201700005C / HL / NHLBI NIH HHS / United States HHSN268201700002C / HB / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States 75N99020D00005 / OF / ORFDO NIH HHS / United States U01 HL072507 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States HHSN268201700003C / HL / NHLBI NIH HHS / United States R01 HL093093 / HL / NHLBI NIH HHS / United States R01 HL087263 / HL / NHLBI NIH HHS / United States HHSN268201700001C / HL / NHLBI NIH HHS / United States R01 MH078143 / MH / NIMH NIH HHS / United States 75N99020D00007 / OF / ORFDO NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States HHSN268201800015I / HB / NHLBI NIH HHS / United States R01 HL071205 / HL / NHLBI NIH HHS / United States U01 HL054481 / HL / NHLBI NIH HHS / United States R03 HL154284 / HL / NHLBI NIH HHS / United States R01 MD012765 / MD / NIMHD NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States HHSN268201700002I / HL / NHLBI NIH HHS / United States HHSN268201700005I / HL / NHLBI NIH HHS / United States 75N98020D00007 / OD / NIH HHS / United States UM1 HG008898 / HG / NHGRI NIH HHS / United States R01 MH083824 / MH / NIMH NIH HHS / United States R01 HL117626 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States R01 HL090682 / HL / NHLBI NIH HHS / United States HHSN268201800005I / HL / NHLBI NIH HHS / United States U24 HG008956 / HG / NHGRI NIH HHS / United States HG011052 / HG / NHGRI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States HHSN268201700003I / HL / NHLBI NIH HHS / United States HHSN268201800006I / HL / NHLBI NIH HHS / United States U01 HL054495 / HL / NHLBI NIH HHS / United States R01 HL071258 / HL / NHLBI NIH HHS / United States R01 AG018728 / AG / NIA NIH HHS / United States R01 HL055673 / HL / NHLBI NIH HHS / United States 75N95020D00004 / DA / NIDA NIH HHS / United States U01 HL054473 / HL / NHLBI NIH HHS / United States 75N99020D00004 / OF / ORFDO NIH HHS / United States K01 HL135405 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States HL007567 / HL / NHLBI NIH HHS / United States R01 HL088119 / HL / NHLBI NIH HHS / United States |
Rare coding variants in RCN3 are associated with blood pressure.
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