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@article{de:2019:aje/kwz005,
author = {de, Vries PS and Brown, MR and Bentley, AR and Sung, YJ and Winkler, TW and Ntalla, I and Schwander, K and Kraja, AT and Guo, X and Franceschini, N and Cheng, C-Y and Sim, X and Vojinovic, D and Huffman, JE and Musani, SK and Li, C and Feitosa, MF and Richard, MA and Noordam, R and Aschard, H and Bartz, TM and Bielak, LF and Deng, X and Dorajoo, R and Lohman, KK and Manning, AK and Rankinen, T and Smith, AV and Tajuddin, SM and Evangelou, E and Graff, M and Alver, M and Boissel, M and Chai, JF and Chen, X and Divers, J and Gandin, I and Gao, C and Goel, A and Hagemeijer, Y and Harris, SE and Hartwig, FP and He, M and Horimoto, ARVR and Hsu, F-C and Jackson, AU and Kasturiratne, A and Komulainen, P and Kühnel, B and Laguzzi, F and Lee, JH and Luan, J and Lyytikäinen, L-P and Matoba, N and Nolte, IM and Pietzner, M and Riaz, M and Said, MA and Scott, RA and Sofer, T and Stancáková, A and Takeuchi, F and Tayo, BO and van, der Most PJ and Varga, TV and Wang, Y and Ware, EB and Wen, W and Y},
doi = {aje/kwz005},
journal = {American Journal of Epidemiology},
pages = {1033--1054},
title = {Multi-ancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions},
url = {http://dx.doi.org/10.1093/aje/kwz005},
volume = {188},
year = {2019}
}

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TY  - JOUR
AB  - An individual's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multi-ancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in Stage 1 (genome-wide discovery) and 66 studies in Stage 2 (focused follow-up), for a total of 394,584 individuals from five ancestry groups. Genetic main and interaction effects were jointly assessed by a 2 degrees of freedom (DF) test, and a 1 DF test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in Stage 1 and were evaluated in Stage 2, followed by combined analyses of Stage 1 and Stage 2. In the combined analysis of Stage 1 and Stage 2, 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2 DF tests, of which 18 were novel. No genome-wide significant associations were found testing the interaction effect alone. The novel loci included several genes (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.
AU  - de,Vries PS
AU  - Brown,MR
AU  - Bentley,AR
AU  - Sung,YJ
AU  - Winkler,TW
AU  - Ntalla,I
AU  - Schwander,K
AU  - Kraja,AT
AU  - Guo,X
AU  - Franceschini,N
AU  - Cheng,C-Y
AU  - Sim,X
AU  - Vojinovic,D
AU  - Huffman,JE
AU  - Musani,SK
AU  - Li,C
AU  - Feitosa,MF
AU  - Richard,MA
AU  - Noordam,R
AU  - Aschard,H
AU  - Bartz,TM
AU  - Bielak,LF
AU  - Deng,X
AU  - Dorajoo,R
AU  - Lohman,KK
AU  - Manning,AK
AU  - Rankinen,T
AU  - Smith,AV
AU  - Tajuddin,SM
AU  - Evangelou,E
AU  - Graff,M
AU  - Alver,M
AU  - Boissel,M
AU  - Chai,JF
AU  - Chen,X
AU  - Divers,J
AU  - Gandin,I
AU  - Gao,C
AU  - Goel,A
AU  - Hagemeijer,Y
AU  - Harris,SE
AU  - Hartwig,FP
AU  - He,M
AU  - Horimoto,ARVR
AU  - Hsu,F-C
AU  - Jackson,AU
AU  - Kasturiratne,A
AU  - Komulainen,P
AU  - Kühnel,B
AU  - Laguzzi,F
AU  - Lee,JH
AU  - Luan,J
AU  - Lyytikäinen,L-P
AU  - Matoba,N
AU  - Nolte,IM
AU  - Pietzner,M
AU  - Riaz,M
AU  - Said,MA
AU  - Scott,RA
AU  - Sofer,T
AU  - Stancáková,A
AU  - Takeuchi,F
AU  - Tayo,BO
AU  - van,der Most PJ
AU  - Varga,TV
AU  - Wang,Y
AU  - Ware,EB
AU  - Wen,W
AU  - Yanek,LR
AU  - Zhang,W
AU  - Zhao,JH
AU  - Afaq,S
AU  - Amin,N
AU  - Amini,M
AU  - Arking,DE
AU  - Aung,T
AU  - Ballantyne,C
AU  - Boerwinkle,E
AU  - Broeckel,U
AU  - Campbell,A
AU  - Canouil,M
AU  - Charumathi,S
AU  - Chen,Y-DI
AU  - Connell,JM
AU  - de,Faire U
AU  - de,Las Fuentes L
AU  - de,Mutsert R
AU  - de,Silva HJ
AU  - Ding,J
AU  - Dominiczak,AF
AU  - Duan,Q
AU  - Eaton,CB
AU  - Eppinga,RN
AU  - Faul,JD
AU  - Fisher,V
AU  - Forrester,T
AU  - Franco,OH
AU  - Friedlander,Y
AU  - Ghanbari,M
AU  - Giulianini,F
AU  - Grabe,HJ
AU  - Grove,ML
AU  - Gu,CC
AU  - Harris,TB
AU  - Heikkinen,S
AU  - Heng,C-K
AU  - Hirata,M
AU  - Hixson,JE
AU  - Howard,BV
AU  - Ikram,MA
AU  - InterAct,Consortium
AU  - Jacobs,DR
AU  - Johnson,C
AU  - Jonas,JB
AU  - Kammerer,CM
AU  - Katsuya,T
AU  - Khor,CC
AU  - Kilpeläinen,TO
AU  - Koh,W-P
AU  - Koistinen,HA
AU  - Kolcic,I
AU  - Kooperberg,C
AU  - Krieger,JE
AU  - Kritchevsky,SB
AU  - Kubo,M
AU  - Kuusisto,J
AU  - Lakka,TA
AU  - Langefeld,CD
AU  - Langenberg,C
AU  - Launer,LJ
AU  - Lehne,B
AU  - Lemaitre,RN
AU  - Li,Y
AU  - Liang,J
AU  - Liu,J
AU  - Liu,K
AU  - Loh,M
AU  - Louie,T
AU  - Mägi,R
AU  - Manichaikul,AW
AU  - McKenzie,CA
AU  - Meitinger,T
AU  - Metspalu,A
AU  - Milaneschi,Y
AU  - Milani,L
AU  - Mohlke,KL
AU  - Mosley,TH
AU  - Mukamal,KJ
AU  - Nalls,MA
AU  - Nauck,M
AU  - Nelson,CP
AU  - Sotoodehnia,N
AU  - O'Connell,JR
AU  - Palmer,ND
AU  - Pazoki,R
AU  - Pedersen,NL
AU  - Peters,A
AU  - Peyser,PA
AU  - Polasek,O
AU  - Poulter,N
AU  - Raffel,LJ
AU  - Raitakari,OT
AU  - Reiner,AP
AU  - Rice,TK
AU  - Rich,SS
AU  - Robino,A
AU  - Robinson,JG
AU  - Rose,LM
AU  - Rudan,I
AU  - Schmidt,CO
AU  - Schreiner,PJ
AU  - Scott,WR
AU  - Sever,P
AU  - Shi,Y
AU  - Sidney,S
AU  - Sims,M
AU  - Smith,BH
AU  - Smith,JA
AU  - Snieder,H
AU  - Starr,JM
AU  - Strauch,K
AU  - Tan,N
AU  - Taylor,KD
DO  - aje/kwz005
EP  - 1054
PY  - 2019///
SN  - 1476-6256
SP  - 1033
TI  - Multi-ancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions
T2  - American Journal of Epidemiology
UR  - http://dx.doi.org/10.1093/aje/kwz005
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30698716
UR  - https://academic.oup.com/aje/article/188/6/1033/5304469
UR  - http://hdl.handle.net/10044/1/67389
VL  - 188
ER  -

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