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GWAS Study

The trans-ancestral genomic architecture of glycemic traits.

Chen J, Spracklen CN, Marenne G et al.

34059833 PubMed ID
GWAS Study Type
1431 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

CJ
Chen J
SC
Spracklen CN
MG
Marenne G
VA
Varshney A
CL
Corbin LJ
LJ
Luan J
WS
Willems SM
WY
Wu Y
ZX
Zhang X
HM
Horikoshi M
BT
Boutin TS
MR
Mägi R
WJ
Waage J
LR
Li-Gao R
CK
Chan KHK
YJ
Yao J
AM
Anasanti MD
CA
Chu AY
CA
Claringbould A
HJ
Heikkinen J
HJ
Hong J
HJ
Hottenga JJ
HS
Huo S
KM
Kaakinen MA
LT
Louie T
MW
März W
MH
Moreno-Macias H
NA
Ndungu A
NS
Nelson SC
NI
Nolte IM
NK
North KE
RC
Raulerson CK
RD
Ray D
RR
Rohde R
RD
Rybin D
SC
Schurmann C
SX
Sim X
SL
Southam L
SI
Stewart ID
WC
Wang CA
WY
Wang Y
WP
Wu P
ZW
Zhang W
AT
Ahluwalia TS
AE
Appel EVR
BL
Bielak LF
BJ
Brody JA
BN
Burtt NP
CC
Cabrera CP
CB
Cade BE
CJ
Chai JF
CX
Chai X
CL
Chang LC
CC
Chen CH
CB
Chen BH
CK
Chitrala KN
CY
Chiu YF
DH
de Haan HG
DG
Delgado GE
DA
Demirkan A
DQ
Duan Q
EJ
Engmann J
FS
Fatumo SA
GJ
Gayán J
GF
Giulianini F
GJ
Gong JH
GS
Gustafsson S
HY
Hai Y
HF
Hartwig FP
HJ
He J
HY
Heianza Y
HT
Huang T
HA
Huerta-Chagoya A
HM
Hwang MY
JR
Jensen RA
KT
Kawaguchi T
KK
Kentistou KA
KY
Kim YJ
KM
Kleber ME
KI
Kooner IK
LS
Lai S
LL
Lange LA
LC
Langefeld CD
LM
Lauzon M
LM
Li M
LS
Ligthart S
LJ
Liu J
LM
Loh M
LJ
Long J
LV
Lyssenko V
MM
Mangino M
MC
Marzi C
MM
Montasser ME
NA
Nag A
NM
Nakatochi M
ND
Noce D
NR
Noordam R
PG
Pistis G
PM
Preuss M
RL
Raffield L
RL
Rasmussen-Torvik LJ
RS
Rich SS
RN
Robertson NR
RR
Rueedi R
RK
Ryan K
SS
Sanna S
SR
Saxena R
SK
Schraut KE
SB
Sennblad B
SK
Setoh K
SA
Smith AV
ST
Sparsø T
SR
Strawbridge RJ
TF
Takeuchi F
TJ
Tan J
TS
Trompet S
VD
van den Akker E
VD
van der Most PJ
VN
Verweij N
VM
Vogel M
WH
Wang H
WC
Wang C
WN
Wang N
WH
Warren HR
WW
Wen W
WT
Wilsgaard T
WA
Wong A
WA
Wood AR
XT
Xie T
ZM
Zafarmand MH
ZJ
Zhao JH
ZW
Zhao W
AN
Amin N
AZ
Arzumanyan Z
AA
Astrup A
BS
Bakker SJL
BD
Baldassarre D
BM
Beekman M
BR
Bergman RN
BA
Bertoni A
BM
Blüher M
BL
Bonnycastle LL
BS
Bornstein SR
BD
Bowden DW
CQ
Cai Q
CA
Campbell A
CH
Campbell H
CY
Chang YC
DG
de Geus EJC
DA
Dehghan A
DS
Du S
EG
Eiriksdottir G
FA
Farmaki AE
FM
Frånberg M
FC
Fuchsberger C
GY
Gao Y
GA
Gjesing AP
GA
Goel A
HS
Han S
HC
Hartman CA
HC
Herder C
HA
Hicks AA
HC
Hsieh CH
HW
Hsueh WA
IS
Ichihara S
IM
Igase M
IM
Ikram MA
JW
Johnson WC
JM
Jørgensen ME
JP
Joshi PK
KR
Kalyani RR
KF
Kandeel FR
KT
Katsuya T
KC
Khor CC
KW
Kiess W
KI
Kolcic I
KT
Kuulasmaa T
KJ
Kuusisto J
LK
Läll K
LK
Lam K
LD
Lawlor DA
LN
Lee NR
LR
Lemaitre RN
LH
Li H
LS
Lin SY
LJ
Lindström J
LA
Linneberg A
LJ
Liu J
LC
Lorenzo C
MT
Matsubara T
MF
Matsuda F
MG
Mingrone G
MS
Mooijaart S
MS
Moon S
NT
Nabika T
NG
Nadkarni GN
NJ
Nadler JL
NM
Nelis M
NM
Neville MJ
NJ
Norris JM
OY
Ohyagi Y
PA
Peters A
PP
Peyser PA
PO
Polasek O
QQ
Qi Q
RD
Raven D
RD
Reilly DF
RA
Reiner A
RF
Rivideneira F
RK
Roll K
RI
Rudan I
SC
Sabanayagam C
SK
Sandow K
SN
Sattar N
SA
Schürmann A
SJ
Shi J
SH
Stringham HM
TK
Taylor KD
TT
Teslovich TM
TB
Thuesen B
TP
Timmers PRHJ
TE
Tremoli E
TM
Tsai MY
UA
Uitterlinden A
VD
van Dam RM
VH
van Heemst D
VH
van Hylckama Vlieg A
VV
van Vliet-Ostaptchouk JV
VJ
Vangipurapu J
VH
Vestergaard H
WT
Wang T
WV
Willems van Dijk K
ZT
Zemunik T
AG
Abecasis GR
AL
Adair LS
AC
Aguilar-Salinas CA
AM
Alarcón-Riquelme ME
AP
An P
AL
Aviles-Santa L
BD
Becker DM
BL
Beilin LJ
BS
Bergmann S
BH
Bisgaard H
BC
Black C
BM
Boehnke M
BE
Boerwinkle E
BB
Böhm BO
BK
Bønnelykke K
BD
Boomsma DI
BE
Bottinger EP
BT
Buchanan TA
CM
Canouil M
CM
Caulfield MJ
CJ
Chambers JC
CD
Chasman DI
CY
Chen YI
CC
Cheng CY
CF
Collins FS
CA
Correa A
CF
Cucca F
DS
de Silva HJ
DG
Dedoussis G
ES
Elmståhl S
EM
Evans MK
FE
Ferrannini E
FL
Ferrucci L
FJ
Florez JC
FP
Franks PW
FT
Frayling TM
FP
Froguel P
GB
Gigante B
GM
Goodarzi MO
GP
Gordon-Larsen P
GH
Grallert H
GN
Grarup N
GS
Grimsgaard S
GL
Groop L
GV
Gudnason V
GX
Guo X
HA
Hamsten A
HT
Hansen T
HC
Hayward C
HS
Heckbert SR
HB
Horta BL
HW
Huang W
IE
Ingelsson E
JP
James PS
JM
Jarvelin MR
JJ
Jonas JB
JJ
Jukema JW
KP
Kaleebu P
KR
Kaplan R
KS
Kardia SLR
KN
Kato N
KS
Keinanen-Kiukaanniemi SM
KB
Kim BJ
KM
Kivimaki M
KH
Koistinen HA
KJ
Kooner JS
KA
Körner A
KP
Kovacs P
KD
Kuh D
KM
Kumari M
KZ
Kutalik Z
LM
Laakso M
LT
Lakka TA
LL
Launer LJ
LK
Leander K
LH
Li H
LX
Lin X
LL
Lind L
LC
Lindgren C
LS
Liu S
LR
Loos RJF
MP
Magnusson PKE
MA
Mahajan A
MA
Metspalu A
MD
Mook-Kanamori DO
MT
Mori TA
MP
Munroe PB
NI
Njølstad I
OJ
O'Connell JR
OA
Oldehinkel AJ
OK
Ong KK
PS
Padmanabhan S
PC
Palmer CNA
PN
Palmer ND
PO
Pedersen O
PC
Pennell CE
PD
Porteous DJ
PP
Pramstaller PP
PM
Province MA
PB
Psaty BM
QL
Qi L
RL
Raffel LJ
RR
Rauramaa R
RS
Redline S
RP
Ridker PM
RF
Rosendaal FR
ST
Saaristo TE
SM
Sandhu M
SJ
Saramies J
SN
Schneiderman N
SP
Schwarz P
SL
Scott LJ
SE
Selvin E
SP
Sever P
SX
Shu XO
SP
Slagboom PE
SK
Small KS
SB
Smith BH
SH
Snieder H
ST
Sofer T
ST
Sørensen TIA
ST
Spector TD
SA
Stanton A
SC
Steves CJ
SM
Stumvoll M
SL
Sun L
TY
Tabara Y
TE
Tai ES
TN
Timpson NJ
TA
Tönjes A
TJ
Tuomilehto J
TT
Tusie T
UM
Uusitupa M
VD
van der Harst P
VD
van Duijn C
VV
Vitart V
VP
Vollenweider P
VT
Vrijkotte TGM
WL
Wagenknecht LE
WM
Walker M
WY
Wang YX
WN
Wareham NJ
WR
Watanabe RM
WH
Watkins H
WW
Wei WB
WA
Wickremasinghe AR
WG
Willemsen G
WJ
Wilson JF
WT
Wong TY
WJ
Wu JY
XA
Xiang AH
YL
Yanek LR
YL
Yengo L
YM
Yokota M
ZE
Zeggini E
ZW
Zheng W
ZA
Zonderman AB
RJ
Rotter JI
GA
Gloyn AL
MM
McCarthy MI
DJ
Dupuis J
MJ
Meigs JB
SR
Scott RA
PI
Prokopenko I
LA
Leong A
LC
Liu CT
PS
Parker SCJ
MK
Mohlke KL
LC
Langenberg C
WE
Wheeler E
MA
Morris AP
BI
Barroso I
Chapter II

Abstract

Summary of the research findings

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

1,431 African American individuals

Chapter III

Study Statistics

Key metrics and study information

1431
Total Participants
GWAS
Study Type
No
Replicated
African American or Afro-Caribbean, East Asian, European, Hispanic or Latin American, South Asian, Sub-Saharan African
Ancestry
U.S., Republic of Korea, Netherlands, Sweden, Finland, Denmark, U.K., France, Switzerland, Germany, Singapore, China, Japan, Philippines, Republic of Ireland, Iceland, Greece, Italy, Australia, Croatia, Estonia, Mexico, Sri Lanka, Spain, Norway, Brazil, Uganda
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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Analysis In Progress

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