Association between cognition and gene polymorphisms involved in thrombosis and haemostasis

Terence J Quinn; Jahad Alghamdi; Sandosh Padmanabhan; David J Porteous; Blair H Smith; Lynne Hocking; Ian J Deary; John Gallacher; Martina Messow; David J Stott

doi:10.1007/s11357-015-9820-y

Association between cognition and gene polymorphisms involved in thrombosis and haemostasis

Terence J Quinn, Jahad Alghamdi, Sandosh Padmanabhan, David J Porteous, Blair H Smith, Lynne Hocking, Ian J Deary, John Gallacher, Martina Messow, David J Stott

Applied Medicine

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

3 Citations (Scopus)

Abstract

An association between blood markers of thrombosis and haemostasis and cognitive decline has been described. These results may be confounded by lifestyle and environmental factors. We used a Mendelian randomisation approach to describe the association between thrombosis/haemostasis genotypes and cognition. We studied the genetic variants (single nucleotide polymorphisms) of circulating markers of thrombosis and haemostasis. Our chosen blood factors and associated polymorphisms were D-dimer [rs12029080], fibrinogen [rs1800789], plasminogen activator inhibitor [rs2227631], and von Willebrand factor [rs1063857]. We described association with multidomain cognitive test scores using data from the Scottish Family Health Study. Cognitive data were analysed for individual tests and combined to give a general cognitive factor. In 20,288 subjects, we found no evidence of association between cognitive function (individual tests and combined scores) and any of the above-mentioned single nucleotide polymorphisms. Lower scores on cognitive measures were associated with increasing age, socioeconomic deprivation, blood pressure, waist-hip ratio, smoking, and vascular comorbidity (all p < 0.001). In a post hoc sensitivity analysis restricted to those aged over 50 years, there was still no signal of association. Our data add to our understanding of determinants of cognition but are not definitive; the variation in blood levels explained by SNPs was modest and our sample size may have been insufficient to detect a modest association.

Original language	English
Article number	80
Number of pages	9
Journal	Age
Volume	37
Issue number	4
Early online date	1 Aug 2015
DOIs	https://doi.org/10.1007/s11357-015-9820-y
Publication status	Published - Aug 2015

Bibliographical note

Acknowledgments Dr. Quinn designed the research study, assisted with analysis and drafted the manuscript. Dr. Alghamdi assisted with genotyping and drafting of the manuscript. Prof Padmanabhan, Porteus, Smith and Hocking assisted with collection and processing of samples. Prof Deary, Gallacher and Stott assisted with supervision, analysis of cognitive data, interpretation of data and drafting of the manuscript. Dr. Messow performed the statistical analyses and assisted with drafting of the manuscript.

Sources of funding This work was supported by the Academy of Medical Sciences, UK. Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. Dr. Quinn is supported by a joint Stroke Association / Chief Scientist Office Senior Clinical Lectureship

Keywords

cognition disorders
dementia
haemostasis
genomics
Mendelian randomization analysis

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Cite this

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title = "Association between cognition and gene polymorphisms involved in thrombosis and haemostasis",

abstract = "An association between blood markers of thrombosis and haemostasis and cognitive decline has been described. These results may be confounded by lifestyle and environmental factors. We used a Mendelian randomisation approach to describe the association between thrombosis/haemostasis genotypes and cognition. We studied the genetic variants (single nucleotide polymorphisms) of circulating markers of thrombosis and haemostasis. Our chosen blood factors and associated polymorphisms were D-dimer [rs12029080], fibrinogen [rs1800789], plasminogen activator inhibitor [rs2227631], and von Willebrand factor [rs1063857]. We described association with multidomain cognitive test scores using data from the Scottish Family Health Study. Cognitive data were analysed for individual tests and combined to give a general cognitive factor. In 20,288 subjects, we found no evidence of association between cognitive function (individual tests and combined scores) and any of the above-mentioned single nucleotide polymorphisms. Lower scores on cognitive measures were associated with increasing age, socioeconomic deprivation, blood pressure, waist-hip ratio, smoking, and vascular comorbidity (all p < 0.001). In a post hoc sensitivity analysis restricted to those aged over 50 years, there was still no signal of association. Our data add to our understanding of determinants of cognition but are not definitive; the variation in blood levels explained by SNPs was modest and our sample size may have been insufficient to detect a modest association.",

keywords = "cognition disorders, dementia, haemostasis, genomics, Mendelian randomization analysis",

author = "Quinn, {Terence J} and Jahad Alghamdi and Sandosh Padmanabhan and Porteous, {David J} and Smith, {Blair H} and Lynne Hocking and Deary, {Ian J} and John Gallacher and Martina Messow and Stott, {David J}",

note = "Acknowledgments Dr. Quinn designed the research study, assisted with analysis and drafted the manuscript. Dr. Alghamdi assisted with genotyping and drafting of the manuscript. Prof Padmanabhan, Porteus, Smith and Hocking assisted with collection and processing of samples. Prof Deary, Gallacher and Stott assisted with supervision, analysis of cognitive data, interpretation of data and drafting of the manuscript. Dr. Messow performed the statistical analyses and assisted with drafting of the manuscript. Sources of funding This work was supported by the Academy of Medical Sciences, UK. Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. Dr. Quinn is supported by a joint Stroke Association / Chief Scientist Office Senior Clinical Lectureship",

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doi = "10.1007/s11357-015-9820-y",

language = "English",

volume = "37",

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AU - Quinn, Terence J

AU - Alghamdi, Jahad

AU - Padmanabhan, Sandosh

AU - Porteous, David J

AU - Smith, Blair H

AU - Hocking, Lynne

AU - Deary, Ian J

AU - Gallacher, John

AU - Messow, Martina

AU - Stott, David J

N1 - Acknowledgments Dr. Quinn designed the research study, assisted with analysis and drafted the manuscript. Dr. Alghamdi assisted with genotyping and drafting of the manuscript. Prof Padmanabhan, Porteus, Smith and Hocking assisted with collection and processing of samples. Prof Deary, Gallacher and Stott assisted with supervision, analysis of cognitive data, interpretation of data and drafting of the manuscript. Dr. Messow performed the statistical analyses and assisted with drafting of the manuscript. Sources of funding This work was supported by the Academy of Medical Sciences, UK. Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates CZD/16/6 and the Scottish Funding Council HR03006. Dr. Quinn is supported by a joint Stroke Association / Chief Scientist Office Senior Clinical Lectureship

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N2 - An association between blood markers of thrombosis and haemostasis and cognitive decline has been described. These results may be confounded by lifestyle and environmental factors. We used a Mendelian randomisation approach to describe the association between thrombosis/haemostasis genotypes and cognition. We studied the genetic variants (single nucleotide polymorphisms) of circulating markers of thrombosis and haemostasis. Our chosen blood factors and associated polymorphisms were D-dimer [rs12029080], fibrinogen [rs1800789], plasminogen activator inhibitor [rs2227631], and von Willebrand factor [rs1063857]. We described association with multidomain cognitive test scores using data from the Scottish Family Health Study. Cognitive data were analysed for individual tests and combined to give a general cognitive factor. In 20,288 subjects, we found no evidence of association between cognitive function (individual tests and combined scores) and any of the above-mentioned single nucleotide polymorphisms. Lower scores on cognitive measures were associated with increasing age, socioeconomic deprivation, blood pressure, waist-hip ratio, smoking, and vascular comorbidity (all p < 0.001). In a post hoc sensitivity analysis restricted to those aged over 50 years, there was still no signal of association. Our data add to our understanding of determinants of cognition but are not definitive; the variation in blood levels explained by SNPs was modest and our sample size may have been insufficient to detect a modest association.

AB - An association between blood markers of thrombosis and haemostasis and cognitive decline has been described. These results may be confounded by lifestyle and environmental factors. We used a Mendelian randomisation approach to describe the association between thrombosis/haemostasis genotypes and cognition. We studied the genetic variants (single nucleotide polymorphisms) of circulating markers of thrombosis and haemostasis. Our chosen blood factors and associated polymorphisms were D-dimer [rs12029080], fibrinogen [rs1800789], plasminogen activator inhibitor [rs2227631], and von Willebrand factor [rs1063857]. We described association with multidomain cognitive test scores using data from the Scottish Family Health Study. Cognitive data were analysed for individual tests and combined to give a general cognitive factor. In 20,288 subjects, we found no evidence of association between cognitive function (individual tests and combined scores) and any of the above-mentioned single nucleotide polymorphisms. Lower scores on cognitive measures were associated with increasing age, socioeconomic deprivation, blood pressure, waist-hip ratio, smoking, and vascular comorbidity (all p < 0.001). In a post hoc sensitivity analysis restricted to those aged over 50 years, there was still no signal of association. Our data add to our understanding of determinants of cognition but are not definitive; the variation in blood levels explained by SNPs was modest and our sample size may have been insufficient to detect a modest association.

KW - cognition disorders

KW - dementia

KW - haemostasis

KW - genomics

KW - Mendelian randomization analysis

U2 - 10.1007/s11357-015-9820-y

DO - 10.1007/s11357-015-9820-y

M3 - Article

C2 - 26228839

SN - 0161-9152

VL - 37

JO - Age

JF - Age

IS - 4

M1 - 80

ER -

Association between cognition and gene polymorphisms involved in thrombosis and haemostasis

Abstract

Bibliographical note

Keywords

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