Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Research output: Contribution to journal › Journal article › Research › peer-review

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Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits. / LifeLines Cohort Study.

In: Human Genetics and Genomics Advances, Vol. 2, No. 1, 100013, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

LifeLines Cohort Study 2021, 'Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits', Human Genetics and Genomics Advances, vol. 2, no. 1, 100013. https://doi.org/10.1016/j.xhgg.2020.100013

APA

LifeLines Cohort Study (2021). Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits. Human Genetics and Genomics Advances, 2(1), [100013]. https://doi.org/10.1016/j.xhgg.2020.100013

Vancouver

LifeLines Cohort Study. Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits. Human Genetics and Genomics Advances. 2021;2(1). 100013. https://doi.org/10.1016/j.xhgg.2020.100013

Author

LifeLines Cohort Study. / Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits. In: Human Genetics and Genomics Advances. 2021 ; Vol. 2, No. 1.

Bibtex

@article{612cd2a8604747f483c068ff5a1b486d,
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 five 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 and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.",
keywords = "blood pressure, depressive symptoms, gene-environment interaction, genome-wide association study, GWAS, GxE, hypertension, psychosocial factors",
author = "Daokun Sun and Richard, {Melissa A.} 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 Lyytik{\"a}inen, {Leo Pekka} 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 Delaney, {Joseph A.C.} and {Diez Roux}, {Ana V.} and Marcus D{\"o}rr and Faul, {Jessica D.} and Fretts, {Amanda M.} and Gallo, {Linda C.} and {LifeLines Cohort Study}",
note = "Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2021",
doi = "10.1016/j.xhgg.2020.100013",
language = "English",
volume = "2",
journal = "Human Genetics and Genomics Advances",
issn = "2666-2477",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

AU - Sun, Daokun

AU - Richard, Melissa A.

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 - Delaney, Joseph A.C.

AU - Diez Roux, Ana V.

AU - Dörr, Marcus

AU - Faul, Jessica D.

AU - Fretts, Amanda M.

AU - Gallo, Linda C.

AU - LifeLines Cohort Study

N1 - Publisher Copyright: © 2020 The Author(s)

PY - 2021

Y1 - 2021

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 five 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 and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and 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 five 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 and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

KW - blood pressure

KW - depressive symptoms

KW - gene-environment interaction

KW - genome-wide association study

KW - GWAS

KW - GxE

KW - hypertension

KW - psychosocial factors

U2 - 10.1016/j.xhgg.2020.100013

DO - 10.1016/j.xhgg.2020.100013

M3 - Journal article

C2 - 34734193

AN - SCOPUS:85119177602

VL - 2

JO - Human Genetics and Genomics Advances

JF - Human Genetics and Genomics Advances

SN - 2666-2477

IS - 1

M1 - 100013

ER -

ID: 285944586