Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits

Lifelines Cohort Study; Daokun Sun; Melissa Richard; Solomon K Musani; Yun Ju Sung; Thomas W Winkler; Karen Schwander; Jin Fang Chai; Xiuqing Guo; Tuomas O Kilpeläinen; Dina Vojinovic; Hugues Aschard; Traci M Bartz; Lawrence F Bielak; Michael R Brown; Kumaraswamy Chitrala; Fernando P Hartwig; Andrea R V R Horimoto; Yongmei Liu; Alisa K Manning; Raymond Noordam; Albert V Smith; Sarah E Harris; Brigitte Kühnel; Leo-Pekka Lyytikäinen; Ilja M Nolte; Rainer Rauramaa; Peter J van der Most; Rujia Wang; Erin B Ware; Stefan Weiss; Wanqing Wen; Lisa R Yanek; Dan E Arking; Donna K Arnett; Ana Barac; Eric Boerwinkle; Ulrich Broeckel; Aravinda Chakravarti; Yii-Der Ida Chen; L Adrienne Cupples; Martha L Davigulus; Lisa de Las Fuentes; Renée de Mutsert; Paul S de Vries; Catharina C A Hartman; Wei Zhao; Albertine J Oldehinkel; Brenda W J H Penninx; Harold Snieder; Ya-Xing Wang; M Fornage

doi:10.1016/j.xhgg.2020.100013

Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits

Lifelines Cohort Study, Daokun Sun, Melissa Richard, Solomon K Musani, Yun Ju Sung, Thomas W Winkler, Karen Schwander, Jin Fang Chai, Xiuqing Guo, Tuomas O Kilpeläinen, Dina Vojinovic, Hugues Aschard, Traci M Bartz, Lawrence F Bielak, Michael R Brown, Kumaraswamy Chitrala, Fernando P Hartwig, Andrea R V R Horimoto, Yongmei Liu, Alisa K ManningRaymond Noordam, Albert V Smith, Sarah E Harris, Brigitte Kühnel, Leo-Pekka Lyytikäinen, Ilja M Nolte, Rainer Rauramaa, Peter J van der Most, Rujia Wang, Erin B Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Dan E Arking, Donna K Arnett, Ana Barac, Eric Boerwinkle, Ulrich Broeckel, Aravinda Chakravarti, Yii-Der Ida Chen, L Adrienne Cupples, Martha L Davigulus, Lisa de Las Fuentes, Renée de Mutsert, Paul S de Vries, Catharina C A Hartman, Wei Zhao, Albertine J Oldehinkel, Brenda W J H Penninx, Harold Snieder, Ya-Xing Wang, M Fornage^*

^*Corresponding author voor dit werk

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Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

Originele taal-2	English
Tijdschrift	HGG advances
Volume	2
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1016/j.xhgg.2020.100013
Status	Published - 14-jan.-2021

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10.1016/j.xhgg.2020.100013Licentie: CC BY-NC-ND

Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traitsFinal publisher's version, 853 KBLicentie: CC BY-NC-ND

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Lifelines Cohort Study, Sun, D., Richard, M., Musani, S. K., Sung, Y. J., Winkler, T. W., Schwander, K., Chai, J. F., Guo, X., Kilpeläinen, T. O., Vojinovic, D., Aschard, H., Bartz, T. M., Bielak, L. F., Brown, M. R., Chitrala, K., Hartwig, F. P., Horimoto, A. R. V. R., Liu, Y., ... Fornage, M. (2021). Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits. HGG advances, 2(1). https://doi.org/10.1016/j.xhgg.2020.100013

@article{7301c55ed0a1403e927b03ca9961996b,

title = "Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits",

abstract = "Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.",

author = "{Lifelines Cohort Study} and Daokun Sun and Melissa Richard and Musani, {Solomon K} and Sung, {Yun Ju} and Winkler, {Thomas W} and Karen Schwander and Chai, {Jin Fang} and Xiuqing Guo and Kilpel{\"a}inen, {Tuomas O} and Dina Vojinovic and Hugues Aschard and Bartz, {Traci M} and Bielak, {Lawrence F} and Brown, {Michael R} and Kumaraswamy Chitrala and Hartwig, {Fernando P} and Horimoto, {Andrea R V R} and Yongmei Liu and Manning, {Alisa K} and Raymond Noordam and Smith, {Albert V} and Harris, {Sarah E} and Brigitte K{\"u}hnel and Leo-Pekka Lyytik{\"a}inen and Nolte, {Ilja M} and Rainer Rauramaa and {van der Most}, {Peter J} and Rujia Wang and Ware, {Erin B} and Stefan Weiss and Wanqing Wen and Yanek, {Lisa R} and Arking, {Dan E} and Arnett, {Donna K} and Ana Barac and Eric Boerwinkle and Ulrich Broeckel and Aravinda Chakravarti and Chen, {Yii-Der Ida} and Cupples, {L Adrienne} and Davigulus, {Martha L} and {de Las Fuentes}, Lisa and {de Mutsert}, Ren{\'e}e and {de Vries}, {Paul S} and Hartman, {Catharina C A} and Wei Zhao and Oldehinkel, {Albertine J} and Penninx, {Brenda W J H} and Harold Snieder and Ya-Xing Wang and M Fornage",

year = "2021",

month = jan,

day = "14",

doi = "10.1016/j.xhgg.2020.100013",

language = "English",

volume = "2",

journal = "HGG advances",

issn = "2666-2477",

publisher = "American Society for Human Genetics",

number = "1",

}

Lifelines Cohort Study, Sun, D, Richard, M, Musani, SK, Sung, YJ, Winkler, TW, Schwander, K, Chai, JF, Guo, X, Kilpeläinen, TO, Vojinovic, D, Aschard, H, Bartz, TM, Bielak, LF, Brown, MR, Chitrala, K, Hartwig, FP, Horimoto, ARVR, Liu, Y, Manning, AK, Noordam, R, Smith, AV, Harris, SE, Kühnel, B, Lyytikäinen, L-P, Nolte, IM, Rauramaa, R, van der Most, PJ , Wang, R, Ware, EB, Weiss, S, Wen, W, Yanek, LR, Arking, DE, Arnett, DK, Barac, A, Boerwinkle, E, Broeckel, U, Chakravarti, A, Chen, Y-DI, Cupples, LA, Davigulus, ML, de Las Fuentes, L, de Mutsert, R, de Vries, PS, Hartman, CCA, Zhao, W, Oldehinkel, AJ, Penninx, BWJH, Snieder, H, Wang, Y-X & Fornage, M 2021, 'Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits', HGG advances, vol. 2, nr. 1. https://doi.org/10.1016/j.xhgg.2020.100013

TY - JOUR

T1 - Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits

AU - Lifelines Cohort Study

AU - Sun, Daokun

AU - Richard, Melissa

AU - Musani, Solomon K

AU - Sung, Yun Ju

AU - Winkler, Thomas W

AU - Schwander, Karen

AU - Chai, Jin Fang

AU - Guo, Xiuqing

AU - Kilpeläinen, Tuomas O

AU - Vojinovic, Dina

AU - Aschard, Hugues

AU - Bartz, Traci M

AU - Bielak, Lawrence F

AU - Brown, Michael R

AU - Chitrala, Kumaraswamy

AU - Hartwig, Fernando P

AU - Horimoto, Andrea R V R

AU - Liu, Yongmei

AU - Manning, Alisa K

AU - Noordam, Raymond

AU - Smith, Albert V

AU - Harris, Sarah E

AU - Kühnel, Brigitte

AU - Lyytikäinen, Leo-Pekka

AU - Nolte, Ilja M

AU - Rauramaa, Rainer

AU - van der Most, Peter J

AU - Wang, Rujia

AU - Ware, Erin B

AU - Weiss, Stefan

AU - Wen, Wanqing

AU - Yanek, Lisa R

AU - Arking, Dan E

AU - Arnett, Donna K

AU - Barac, Ana

AU - Boerwinkle, Eric

AU - Broeckel, Ulrich

AU - Chakravarti, Aravinda

AU - Chen, Yii-Der Ida

AU - Cupples, L Adrienne

AU - Davigulus, Martha L

AU - de Las Fuentes, Lisa

AU - de Mutsert, Renée

AU - de Vries, Paul S

AU - Hartman, Catharina C A

AU - Zhao, Wei

AU - Oldehinkel, Albertine J

AU - Penninx, Brenda W J H

AU - Snieder, Harold

AU - Wang, Ya-Xing

AU - Fornage, M

PY - 2021/1/14

Y1 - 2021/1/14

N2 - Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

AB - Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

U2 - 10.1016/j.xhgg.2020.100013

DO - 10.1016/j.xhgg.2020.100013

M3 - Article

C2 - 34734193

SN - 2666-2477

VL - 2

JO - HGG advances

JF - HGG advances

IS - 1

ER -

Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits

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