Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. / Feitosa, Mary F; Kraja, Aldi T; Chasman, Daniel I; Sung, Yun J; Winkler, Thomas W; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K; Li, Changwei; Bentley, Amy R; Brown, Michael R; Schwander, Karen; Richard, Melissa A; Noordam, Raymond; Aschard, Hugues; Bartz, Traci M; Bielak, Lawrence F; Dorajoo, Rajkumar; Fisher, Virginia; Hartwig, Fernando P; Horimoto, Andrea R V R; Lohman, Kurt K; Manning, Alisa K; Rankinen, Tuomo; Smith, Albert V; Tajuddin, Salman M; Wojczynski, Mary K; Alver, Maris; Boissel, Mathilde; Cai, Qiuyin; Campbell, Archie; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gao, Chuan; Goel, Anuj; Hagemeijer, Yanick; Harris, Sarah E; He, Meian; Hsu, Fang-Chi; Jackson, Anne U; Kähönen, Mika; Zhao, Jing Hua; Kilpeläinen, Tuomas O.; Christensen, Kaare; V Varga, Tibor.
In: PLoS ONE, Vol. 13, No. 6, e0198166, 2018, p. 1-36.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
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
AU - V Varga, Tibor
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
VL - 13
SP - 1
EP - 36
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 6
M1 - e0198166
ER -
ID: 201906283