Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.

TitleLeveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.
Publication TypeJournal Article
Year of Publication2019
AuthorsHe, KY, Li, X, Kelly, TN, Liang, J, Cade, BE, Assimes, TL, Becker, LC, Beitelshees, AL, Bress, AP, Chang, Y-PChristy, Chen, Y-DIda, de Vries, PS, Fox, ER, Franceschini, N, Furniss, A, Gao, Y, Guo, X, Haessler, J, Hwang, S-J, Irvin, MRyan, Kalyani, RR, Liu, C-T, Liu, C, Martin, LWarsinger, Montasser, ME, Muntner, PM, Mwasongwe, S, Palmas, W, Reiner, AP, Shimbo, D, Smith, JA, Snively, BM, Yanek, LR, Boerwinkle, E, Correa, A, L Cupples, A, He, J, Kardia, SLR, Kooperberg, C, Mathias, RA, Mitchell, BD, Psaty, BM, Vasan, RS, Rao, DC, Rich, SS, Rotter, JI, Wilson, JG, Chakravarti, A, Morrison, AC, Levy, D, Arnett, DK, Redline, S, Zhu, X
Corporate AuthorsNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Blood Pressure Working Group
JournalHum Genet
Volume138
Issue2
Pagination199-210
Date Published2019 Feb
ISSN1432-1203
KeywordsAlternative Splicing, Blood Pressure, Chromosomes, Human, Pair 16, Exome, Female, Follow-Up Studies, Genetic Linkage, Genetic Variation, Genome, Human, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Male, Recombinases, RNA Splicing Factors
Abstract

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p 
DOI10.1007/s00439-019-01975-0
Alternate JournalHum Genet
PubMed ID30671673
PubMed Central IDPMC6404531
Grant ListR01 HG003054 / HG / NHGRI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL055673 / HL / NHLBI NIH HHS / United States
HHSN268201100037C / HL / NHLBI NIH HHS / United States
R01 HL071025 / HL / NHLBI NIH HHS / United States
R01 HL112064 / HL / NHLBI NIH HHS / United States
HL113338 / HL / NHLBI NIH HHS / United States
K01 HL133468 / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL087698 / HL / NHLBI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
R01 HL121007 / HL / NHLBI NIH HHS / United States
HHSN268201600002C / HL / NHLBI NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201600018C / HL / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
U10 HL054464 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
R01 DK117445 / DK / NIDDK NIH HHS / United States
R01 HL088120 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI 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
N01HC95168 / HL / NHLBI NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
U10 HL054481 / HL / NHLBI NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
R01 HL098433 / HL / NHLBI NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
HHSN268201700001I / HL / NHLBI 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
HHSN268201700004I / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
M01 RR000052 / RR / NCRR 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
HHSN268201600004C / HL / NHLBI NIH HHS / United States
U01 HL072515 / HL / NHLBI NIH HHS / United States
U01 HL072518 / HL / NHLBI NIH HHS / United States
HG003054 / HG / NHGRI NIH HHS / United States
HHSN268201500014C / HL / NHLBI NIH HHS / United States
HHSN268201600001C / HL / NHLBI NIH HHS / United States
HL086694 / HL / NHLBI NIH HHS / United States
R01 HL087263 / HL / NHLBI NIH HHS / United States
U01 HL072507 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
U01 HL054481 / HL / NHLBI NIH HHS / United States
R01 MD012765 / MD / NIMHD NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
T32 HL007567 / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
P20 GM121334 / GM / NIGMS NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
T32 DK091317 / DK / NIDDK NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 HL090682 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
U54 GM115428 / GM / NIGMS NIH HHS / United States
R01 AG018728 / AG / NIA NIH HHS / United States
K01 HL135405 / HL / NHLBI NIH HHS / United States
R01 HL088119 / HL / NHLBI NIH HHS / United States