Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study

Minghua Liu; Farid Khasiyev; Sanjeev Sariya; Antonio Spagnolo-Allende; Danurys L Sanchez; Howard Andrews; Qiong Yang; Alexa Beiser; Ye Qiao; Emy A Thomas; Jose Rafael Romero; Tatjana Rundek; Adam M Brickman; Jennifer J Manly; Mitchell Sv Elkind; Sudha Seshadri; Christopher Chen; Ralph L Sacco; Saima Hilal; Bruce A Wasserman; Giuseppe Tosto; Myriam Fornage; Jose Gutierrez

doi:10.1101/2023.01.31.23285251

Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study

Minghua Liu, Farid Khasiyev, Sanjeev Sariya, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Emy A Thomas, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Ralph L Sacco, Saima Hilal, Bruce A WassermanGiuseppe Tosto, Myriam Fornage, Jose Gutierrez

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Brain arterial diameters are novel imaging biomarkers of cerebrovascular disease, cognitive decline and dementia. Traditional vascular risk factors have been associated with brain arterial diameters but whether there may be genetic determinants of brain arterial diameters is unknown.

RESULTS: We studied 4150 participants from six geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). We measured brain arterial diameters for 13 segments and averaged them to obtain a global measure of brain arterial diameters as well as the posterior and anterior circulations. A genome-wide association study (GWAS) revealed 14 variants at one locus associated with global brain arterial diameter at genome-wide significance (P<5×10 -8 ) (top SNP, rs7921574; β =0.06, P=1.54×10 -8 ). This locus mapped to an intron of CNNM2 . A trans-ancestry GWAS meta-analysis identified two more loci at NT5C2 (rs10748839; P=2.54×10 -8 ) and at AS3MT (rs10786721; P=4.97×10 -8 ), associated with global brain arterial diameter. In addition, two SNPs co-localized with expression of CNNM2 (rs7897654, β=0.12, P=6.17×10 -7 ) and AL356608 . 1 (rs10786719, β =-0.17, P=6.60×10 -6 ) in brain tissue. For the posterior brain arterial diameter, two variants at one locus mapped to an intron of TCF25 were identified (top SNP, rs35994878; β =0.11, P=2.94×10 -8 ). For the anterior brain arterial diameter, one locus at ADAP1 was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10 -8 ).

CONCLUSION: Our study reveals three novel risk loci (CNNM2, NT5C2 and AS3MT) associated with brain arterial diameters. Our finding may elucidate the mechanisms by which brain arterial diameters influence the risk of stroke and dementia.

Original language	English (US)
Journal	medRxiv : the preprint server for health sciences
DOIs	https://doi.org/10.1101/2023.01.31.23285251
State	Published - Feb 15 2023

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Liu, M., Khasiyev, F., Sariya, S., Spagnolo-Allende, A., Sanchez, D. L., Andrews, H., Yang, Q., Beiser, A., Qiao, Y., Thomas, E. A., Romero, J. R., Rundek, T., Brickman, A. M., Manly, J. J., Elkind, M. S., Seshadri, S., Chen, C., Sacco, R. L., Hilal, S., ... Gutierrez, J. (2023). Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2023.01.31.23285251

Liu, M, Khasiyev, F, Sariya, S, Spagnolo-Allende, A, Sanchez, DL, Andrews, H, Yang, Q, Beiser, A, Qiao, Y, Thomas, EA, Romero, JR, Rundek, T, Brickman, AM, Manly, JJ, Elkind, MS, Seshadri, S, Chen, C, Sacco, RL, Hilal, S, Wasserman, BA, Tosto, G, Fornage, M & Gutierrez, J 2023, 'Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study', medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2023.01.31.23285251

@article{7e80e6daefdf4da08063fa4cc5e61da8,

title = "Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study",

abstract = "BACKGROUND: Brain arterial diameters are novel imaging biomarkers of cerebrovascular disease, cognitive decline and dementia. Traditional vascular risk factors have been associated with brain arterial diameters but whether there may be genetic determinants of brain arterial diameters is unknown.RESULTS: We studied 4150 participants from six geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). We measured brain arterial diameters for 13 segments and averaged them to obtain a global measure of brain arterial diameters as well as the posterior and anterior circulations. A genome-wide association study (GWAS) revealed 14 variants at one locus associated with global brain arterial diameter at genome-wide significance (P<5×10 -8 ) (top SNP, rs7921574; β =0.06, P=1.54×10 -8 ). This locus mapped to an intron of CNNM2 . A trans-ancestry GWAS meta-analysis identified two more loci at NT5C2 (rs10748839; P=2.54×10 -8 ) and at AS3MT (rs10786721; P=4.97×10 -8 ), associated with global brain arterial diameter. In addition, two SNPs co-localized with expression of CNNM2 (rs7897654, β=0.12, P=6.17×10 -7 ) and AL356608 . 1 (rs10786719, β =-0.17, P=6.60×10 -6 ) in brain tissue. For the posterior brain arterial diameter, two variants at one locus mapped to an intron of TCF25 were identified (top SNP, rs35994878; β =0.11, P=2.94×10 -8 ). For the anterior brain arterial diameter, one locus at ADAP1 was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10 -8 ). CONCLUSION: Our study reveals three novel risk loci (CNNM2, NT5C2 and AS3MT) associated with brain arterial diameters. Our finding may elucidate the mechanisms by which brain arterial diameters influence the risk of stroke and dementia.",

author = "Minghua Liu and Farid Khasiyev and Sanjeev Sariya and Antonio Spagnolo-Allende and Sanchez, {Danurys L} and Howard Andrews and Qiong Yang and Alexa Beiser and Ye Qiao and Thomas, {Emy A} and Romero, {Jose Rafael} and Tatjana Rundek and Brickman, {Adam M} and Manly, {Jennifer J} and Elkind, {Mitchell Sv} and Sudha Seshadri and Christopher Chen and Sacco, {Ralph L} and Saima Hilal and Wasserman, {Bruce A} and Giuseppe Tosto and Myriam Fornage and Jose Gutierrez",

year = "2023",

month = feb,

day = "15",

doi = "10.1101/2023.01.31.23285251",

language = "English (US)",

journal = "medRxiv : the preprint server for health sciences",

}

TY - JOUR

T1 - Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations

T2 - A Genome-Wide Association Study

AU - Liu, Minghua

AU - Khasiyev, Farid

AU - Sariya, Sanjeev

AU - Spagnolo-Allende, Antonio

AU - Sanchez, Danurys L

AU - Andrews, Howard

AU - Yang, Qiong

AU - Beiser, Alexa

AU - Qiao, Ye

AU - Thomas, Emy A

AU - Romero, Jose Rafael

AU - Rundek, Tatjana

AU - Brickman, Adam M

AU - Manly, Jennifer J

AU - Elkind, Mitchell Sv

AU - Seshadri, Sudha

AU - Chen, Christopher

AU - Sacco, Ralph L

AU - Hilal, Saima

AU - Wasserman, Bruce A

AU - Tosto, Giuseppe

AU - Fornage, Myriam

AU - Gutierrez, Jose

PY - 2023/2/15

Y1 - 2023/2/15

N2 - BACKGROUND: Brain arterial diameters are novel imaging biomarkers of cerebrovascular disease, cognitive decline and dementia. Traditional vascular risk factors have been associated with brain arterial diameters but whether there may be genetic determinants of brain arterial diameters is unknown.RESULTS: We studied 4150 participants from six geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). We measured brain arterial diameters for 13 segments and averaged them to obtain a global measure of brain arterial diameters as well as the posterior and anterior circulations. A genome-wide association study (GWAS) revealed 14 variants at one locus associated with global brain arterial diameter at genome-wide significance (P<5×10 -8 ) (top SNP, rs7921574; β =0.06, P=1.54×10 -8 ). This locus mapped to an intron of CNNM2 . A trans-ancestry GWAS meta-analysis identified two more loci at NT5C2 (rs10748839; P=2.54×10 -8 ) and at AS3MT (rs10786721; P=4.97×10 -8 ), associated with global brain arterial diameter. In addition, two SNPs co-localized with expression of CNNM2 (rs7897654, β=0.12, P=6.17×10 -7 ) and AL356608 . 1 (rs10786719, β =-0.17, P=6.60×10 -6 ) in brain tissue. For the posterior brain arterial diameter, two variants at one locus mapped to an intron of TCF25 were identified (top SNP, rs35994878; β =0.11, P=2.94×10 -8 ). For the anterior brain arterial diameter, one locus at ADAP1 was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10 -8 ). CONCLUSION: Our study reveals three novel risk loci (CNNM2, NT5C2 and AS3MT) associated with brain arterial diameters. Our finding may elucidate the mechanisms by which brain arterial diameters influence the risk of stroke and dementia.

AB - BACKGROUND: Brain arterial diameters are novel imaging biomarkers of cerebrovascular disease, cognitive decline and dementia. Traditional vascular risk factors have been associated with brain arterial diameters but whether there may be genetic determinants of brain arterial diameters is unknown.RESULTS: We studied 4150 participants from six geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). We measured brain arterial diameters for 13 segments and averaged them to obtain a global measure of brain arterial diameters as well as the posterior and anterior circulations. A genome-wide association study (GWAS) revealed 14 variants at one locus associated with global brain arterial diameter at genome-wide significance (P<5×10 -8 ) (top SNP, rs7921574; β =0.06, P=1.54×10 -8 ). This locus mapped to an intron of CNNM2 . A trans-ancestry GWAS meta-analysis identified two more loci at NT5C2 (rs10748839; P=2.54×10 -8 ) and at AS3MT (rs10786721; P=4.97×10 -8 ), associated with global brain arterial diameter. In addition, two SNPs co-localized with expression of CNNM2 (rs7897654, β=0.12, P=6.17×10 -7 ) and AL356608 . 1 (rs10786719, β =-0.17, P=6.60×10 -6 ) in brain tissue. For the posterior brain arterial diameter, two variants at one locus mapped to an intron of TCF25 were identified (top SNP, rs35994878; β =0.11, P=2.94×10 -8 ). For the anterior brain arterial diameter, one locus at ADAP1 was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10 -8 ). CONCLUSION: Our study reveals three novel risk loci (CNNM2, NT5C2 and AS3MT) associated with brain arterial diameters. Our finding may elucidate the mechanisms by which brain arterial diameters influence the risk of stroke and dementia.

U2 - 10.1101/2023.01.31.23285251

DO - 10.1101/2023.01.31.23285251

M3 - Article

C2 - 36778463

JO - medRxiv : the preprint server for health sciences

JF - medRxiv : the preprint server for health sciences

ER -

Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study

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