Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Mary F Feitosa; Aldi T Kraja; Daniel I Chasman; Yun J Sung; Thomas W Winkler; Ioanna Ntalla; Xiuqing Guo; Nora Franceschini; Ching-Yu Cheng; Xueling Sim; Dina Vojinovic; Jonathan Marten; Solomon K Musani; Changwei Li; Amy R Bentley; Michael R Brown; Karen Schwander; Melissa A Richard; Raymond Noordam; Hugues Aschard; Traci M Bartz; Lawrence F Bielak; Rajkumar Dorajoo; Virginia Fisher; Fernando P Hartwig; Andrea R V R Horimoto; Kurt K Lohman; Alisa K Manning; Tuomo Rankinen; Albert V Smith; Salman M Tajuddin; Mary K Wojczynski; Maris Alver; Mathilde Boissel; Qiuyin Cai; Archie Campbell; Jin Fang Chai; Xu Chen; Jasmin Divers; Chuan Gao; Anuj Goel; Yanick Hagemeijer; Sarah E Harris; Meian He; Fang-Chi Hsu; Anne U Jackson; Mika Kähönen; Jing Hua Zhao; Tuomas O. Kilpeläinen; Kaare Christensen

doi:10.1371/journal.pone.0198166

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Mary F Feitosa, Aldi T Kraja, Daniel I Chasman, Yun J Sung, Thomas W Winkler, Ioanna Ntalla, Xiuqing Guo, Nora Franceschini, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jonathan Marten, Solomon K Musani, Changwei Li, Amy R Bentley, Michael R Brown, Karen Schwander, Melissa A Richard, Raymond Noordam, Hugues AschardTraci M Bartz, Lawrence F Bielak, Rajkumar Dorajoo, Virginia Fisher, Fernando P Hartwig, Andrea R V R Horimoto, Kurt K Lohman, Alisa K Manning, Tuomo Rankinen, Albert V Smith, Salman M Tajuddin, Mary K Wojczynski, Maris Alver, Mathilde Boissel, Qiuyin Cai, Archie Campbell, Jin Fang Chai, Xu Chen, Jasmin Divers, Chuan Gao, Anuj Goel, Yanick Hagemeijer, Sarah E Harris, Meian He, Fang-Chi Hsu, Anne U Jackson, Mika Kähönen, Jing Hua Zhao, Tuomas O. Kilpeläinen, Kaare Christensen

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Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Originalsprog	Engelsk
Artikelnummer	e0198166
Tidsskrift	PLoS ONE
Vol/bind	13
Udgave nummer	6
Sider (fra-til)	1-36
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0198166
Status	Udgivet - 2018

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10.1371/journal.pone.0198166

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestriesForlagets udgivne version, 1,6 MB

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Feitosa, M. F., Kraja, A. T., Chasman, D. I., Sung, Y. J., Winkler, T. W., Ntalla, I., Guo, X., Franceschini, N., Cheng, C.-Y., Sim, X., Vojinovic, D., Marten, J., Musani, S. K., Li, C., Bentley, A. R., Brown, M. R., Schwander, K., Richard, M. A., Noordam, R., ... Christensen, K. (2018). Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. PLoS ONE, 13(6), 1-36. Artikel e0198166. https://doi.org/10.1371/journal.pone.0198166

Feitosa, MF, Kraja, AT, Chasman, DI, Sung, YJ, Winkler, TW, Ntalla, I, Guo, X, Franceschini, N, Cheng, C-Y, Sim, X, Vojinovic, D, Marten, J, Musani, SK, Li, C, Bentley, AR, Brown, MR, Schwander, K, Richard, MA, Noordam, R, Aschard, H, Bartz, TM, Bielak, LF, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, ARVR, Lohman, KK, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, SM, Wojczynski, MK, Alver, M, Boissel, M, Cai, Q, Campbell, A, Chai, JF, Chen, X, Divers, J, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, He, M, Hsu, F-C, Jackson, AU, Kähönen, M, Zhao, JH, Kilpeläinen, TO & Christensen, K 2018, 'Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries', PLoS ONE, bind 13, nr. 6, e0198166, s. 1-36. https://doi.org/10.1371/journal.pone.0198166

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title = "Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries",

abstract = "Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.",

author = "Feitosa, {Mary F} and Kraja, {Aldi T} and Chasman, {Daniel I} and Sung, {Yun J} and Winkler, {Thomas W} and Ioanna Ntalla and Xiuqing Guo and Nora Franceschini and Ching-Yu Cheng and Xueling Sim and Dina Vojinovic and Jonathan Marten and Musani, {Solomon K} and Changwei Li and Bentley, {Amy R} and Brown, {Michael R} and Karen Schwander and Richard, {Melissa A} and Raymond Noordam and Hugues Aschard and Bartz, {Traci M} and Bielak, {Lawrence F} and Rajkumar Dorajoo and Virginia Fisher and Hartwig, {Fernando P} and Horimoto, {Andrea R V R} and Lohman, {Kurt K} and Manning, {Alisa K} and Tuomo Rankinen and Smith, {Albert V} and Tajuddin, {Salman M} and Wojczynski, {Mary K} and Maris Alver and Mathilde Boissel and Qiuyin Cai and Archie Campbell and Chai, {Jin Fang} and Xu Chen and Jasmin Divers and Chuan Gao and Anuj Goel and Yanick Hagemeijer and Harris, {Sarah E} and Meian He and Fang-Chi Hsu and Jackson, {Anne U} and Mika K{\"a}h{\"o}nen and Zhao, {Jing Hua} and Kilpel{\"a}inen, {Tuomas O.} and Kaare Christensen",

year = "2018",

doi = "10.1371/journal.pone.0198166",

language = "English",

volume = "13",

pages = "1--36",

journal = "PLoS ONE",

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T1 - Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

AU - Feitosa, Mary F

AU - Kraja, Aldi T

AU - Chasman, Daniel I

AU - Sung, Yun J

AU - Winkler, Thomas W

AU - Ntalla, Ioanna

AU - Guo, Xiuqing

AU - Franceschini, Nora

AU - Cheng, Ching-Yu

AU - Sim, Xueling

AU - Vojinovic, Dina

AU - Marten, Jonathan

AU - Musani, Solomon K

AU - Li, Changwei

AU - Bentley, Amy R

AU - Brown, Michael R

AU - Schwander, Karen

AU - Richard, Melissa A

AU - Noordam, Raymond

AU - Aschard, Hugues

AU - Bartz, Traci M

AU - Bielak, Lawrence F

AU - Dorajoo, Rajkumar

AU - Fisher, Virginia

AU - Hartwig, Fernando P

AU - Horimoto, Andrea R V R

AU - Lohman, Kurt K

AU - Manning, Alisa K

AU - Rankinen, Tuomo

AU - Smith, Albert V

AU - Tajuddin, Salman M

AU - Wojczynski, Mary K

AU - Alver, Maris

AU - Boissel, Mathilde

AU - Cai, Qiuyin

AU - Campbell, Archie

AU - Chai, Jin Fang

AU - Chen, Xu

AU - Divers, Jasmin

AU - Gao, Chuan

AU - Goel, Anuj

AU - Hagemeijer, Yanick

AU - Harris, Sarah E

AU - He, Meian

AU - Hsu, Fang-Chi

AU - Jackson, Anne U

AU - Kähönen, Mika

AU - Zhao, Jing Hua

AU - Kilpeläinen, Tuomas O.

AU - Christensen, Kaare

PY - 2018

Y1 - 2018

N2 - Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

AB - Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

U2 - 10.1371/journal.pone.0198166

DO - 10.1371/journal.pone.0198166

M3 - Journal article

C2 - 29912962

SN - 1932-6203

VL - 13

SP - 1

EP - 36

JO - PLoS ONE

JF - PLoS ONE

IS - 6

M1 - e0198166

ER -

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

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