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Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

Peloso GM, Auer PL, Bis JC et al.

24507774 PubMed ID
GWAS Study Type
56538 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

PG
Peloso GM
AP
Auer PL
BJ
Bis JC
VA
Voorman A
MA
Morrison AC
SN
Stitziel NO
BJ
Brody JA
KS
Khetarpal SA
CJ
Crosby JR
FM
Fornage M
IA
Isaacs A
JJ
Jakobsdottir J
FM
Feitosa MF
DG
Davies G
HJ
Huffman JE
MA
Manichaikul A
DB
Davis B
LK
Lohman K
JA
Joon AY
SA
Smith AV
GM
Grove ML
ZP
Zanoni P
RV
Redon V
DS
Demissie S
LK
Lawson K
PU
Peters U
CC
Carlson C
JR
Jackson RD
RK
Ryckman KK
MR
Mackey RH
RJ
Robinson JG
SD
Siscovick DS
SP
Schreiner PJ
MJ
Mychaleckyj JC
PJ
Pankow JS
HA
Hofman A
UA
Uitterlinden AG
HT
Harris TB
TK
Taylor KD
SJ
Stafford JM
RL
Reynolds LM
MR
Marioni RE
DA
Dehghan A
FO
Franco OH
PA
Patel AP
LY
Lu Y
HG
Hindy G
GO
Gottesman O
BE
Bottinger EP
MO
Melander O
OM
Orho-Melander M
LR
Loos RJ
DS
Duga S
MP
Merlini PA
FM
Farrall M
GA
Goel A
AR
Asselta R
GD
Girelli D
MN
Martinelli N
SS
Shah SH
KW
Kraus WE
LM
Li M
RD
Rader DJ
RM
Reilly MP
MR
McPherson R
WH
Watkins H
AD
Ardissino D
ZQ
Zhang Q
WJ
Wang J
TM
Tsai MY
TH
Taylor HA
CA
Correa A
GM
Griswold ME
LL
Lange LA
SJ
Starr JM
RI
Rudan I
EG
Eiriksdottir G
LL
Launer LJ
OJ
Ordovas JM
LD
Levy D
CY
Chen YD
RA
Reiner AP
HC
Hayward C
PO
Polasek O
DI
Deary IJ
BI
Borecki IB
LY
Liu Y
GV
Gudnason V
WJ
Wilson JG
VD
van Duijn CM
KC
Kooperberg C
RS
Rich SS
PB
Psaty BM
RJ
Rotter JI
OC
O'Donnell CJ
RK
Rice K
BE
Boerwinkle E
KS
Kathiresan S
CL
Cupples LA
Chapter II

Abstract

Summary of the research findings

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.

up to 42,208 European ancestry individuals, up to 14,330 African ancestry individuals

Chapter III

Study Statistics

Key metrics and study information

56538
Total Participants
GWAS
Study Type
No
Replicated
European, African unspecified
Ancestry
U.S., Netherlands, Finland, U.K., Croatia
Recruitment Country
Chapter IV

AI-Generated Summary

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