Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism
Abstract Background The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear. Objective To investigate the joint effect of obesity and a genetic risk score (GRS) composed of established prothrombotic single nucleotide polymo...
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| Veröffentlicht in: | Thrombosis and haemostasis 2022-02, Vol.122 (2), p.267-276 |
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| creator | Frischmuth, Tobias Hindberg, Kristian Gabrielsen, Maiken E. Brumpton, Ben Hveem, Kristian Brækkan, Sigrid K. Hansen, John-Bjarne Morelli, Vânia M. |
| description | Abstract
Background
The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear.
Objective
To investigate the joint effect of obesity and a genetic risk score (GRS) composed of established prothrombotic single nucleotide polymorphisms (SNPs) on VTE risk using a population-based case–cohort.
Methods
Cases with incident VTE (
n
= 1,470) and a subcohort (
n
= 12,826) were derived from the Tromsø Study (1994–2012) and the Trøndelag Health Study (HUNT) (1995–2008). Participants were genotyped for
ABO
(rs8176719),
F5
(rs6025),
F2
(rs1799963),
FGG
(rs2066865), and
F11
(rs2036914) SNPs. Age- and sex-adjusted hazard ratios (HRs) were estimated according to body mass index (BMI) categories and number of risk alleles for individual SNPs and the GRS (0–1, 2, 3, ≥4 alleles).
Results
The combination of obesity (BMI ≥ 30kg/m
2
) and risk alleles, either as individual SNPs or as a GRS, had an additive effect on VTE risk (i.e., no biological interaction). Obese subjects who were carriers of ≥4 risk alleles had a 2.85-fold (95% confidence interval [CI]: 2.05–3.96) increased risk of overall VTE compared with those with BMI |
| doi_str_mv | 10.1055/a-1497-9777 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_3HK</sourceid><recordid>TN_cdi_cristin_nora_10037_24422</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>33940655</sourcerecordid><originalsourceid>FETCH-LOGICAL-c385t-7dde67cbc037e87827202e0bc21e8018fde2374d3d927da720279c1a11963ad63</originalsourceid><addsrcrecordid>eNpt0D1PwzAQBmALgWgpTOzgGRTwRxInI6pKKSoqQgWxRYl9Ud0mcRU7Q_89jkKZGKwb_Nwr3YvQNSUPlETRYx7QMBVBKoQ4QWMWxSKIk_T7FI0JD0kQszAaoQtrt4TQOEyjczTiPA1JHEVjtHs1unF4VpYgHTYlfusqp_cV4PfWuE1r6sI4LfEcGuMOe7A4bxReFWC1O2DTYLcB_KHtrt9dNFIr8HFfXncWr4d98K_Str5EZ2VeWbj6nRP0-TxbT1-C5Wq-mD4tA8mTyAVCKYiFLCThAhKRMMEIA1JIRiEhNCkVMC5CxVXKhMr7X5FKmlOaxjxXMZ-g2yFXtto63WSNafOMEp-XsTBkzIv7ozDWtlBm-1bXeXvwKutLzbz3pWZ9qV7fDHrfFTWoP3ts0YO7AbiNhhqyrenaxl_4b9oPaEd-1Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism</title><source>NORA - Norwegian Open Research Archives</source><creator>Frischmuth, Tobias ; Hindberg, Kristian ; Gabrielsen, Maiken E. ; Brumpton, Ben ; Hveem, Kristian ; Brækkan, Sigrid K. ; Hansen, John-Bjarne ; Morelli, Vânia M.</creator><creatorcontrib>Frischmuth, Tobias ; Hindberg, Kristian ; Gabrielsen, Maiken E. ; Brumpton, Ben ; Hveem, Kristian ; Brækkan, Sigrid K. ; Hansen, John-Bjarne ; Morelli, Vânia M.</creatorcontrib><description>Abstract
Background
The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear.
Objective
To investigate the joint effect of obesity and a genetic risk score (GRS) composed of established prothrombotic single nucleotide polymorphisms (SNPs) on VTE risk using a population-based case–cohort.
Methods
Cases with incident VTE (
n
= 1,470) and a subcohort (
n
= 12,826) were derived from the Tromsø Study (1994–2012) and the Trøndelag Health Study (HUNT) (1995–2008). Participants were genotyped for
ABO
(rs8176719),
F5
(rs6025),
F2
(rs1799963),
FGG
(rs2066865), and
F11
(rs2036914) SNPs. Age- and sex-adjusted hazard ratios (HRs) were estimated according to body mass index (BMI) categories and number of risk alleles for individual SNPs and the GRS (0–1, 2, 3, ≥4 alleles).
Results
The combination of obesity (BMI ≥ 30kg/m
2
) and risk alleles, either as individual SNPs or as a GRS, had an additive effect on VTE risk (i.e., no biological interaction). Obese subjects who were carriers of ≥4 risk alleles had a 2.85-fold (95% confidence interval [CI]: 2.05–3.96) increased risk of overall VTE compared with those with BMI <25 kg/m
2
and 0 to 1 risk allele. However, in subgroups, the combination of obesity and ≥4 risk alleles was more pronounced for deep vein thrombosis (DVT) (HR: 3.20; 95% CI: 2.09–4.90) and unprovoked VTE (HR: 3.82; 95% CI: 2.25–6.47), suggesting a supra-additive effect.
Conclusion
Our findings indicate that the combination of obesity and GRS has an additive effect on the risk of overall VTE. However, it may have a supra-additive effect on the risk of DVT and unprovoked VTE.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1055/a-1497-9777</identifier><identifier>PMID: 33940655</identifier><language>eng</language><publisher>Rüdigerstraße 14, 70469 Stuttgart, Germany: Georg Thieme Verlag KG</publisher><subject>Alleles ; Female ; Fibrinogen - genetics ; Genotype ; Humans ; Male ; Middle Aged ; Norway ; Obesity - genetics ; Polymorphism, Single Nucleotide ; Prothrombin - genetics ; Risk Factors ; Stroke, Systemic or Venous Thromboembolism ; Venous Thromboembolism - epidemiology ; Venous Thromboembolism - genetics</subject><ispartof>Thrombosis and haemostasis, 2022-02, Vol.122 (2), p.267-276</ispartof><rights>Thieme. All rights reserved.</rights><rights>info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-7dde67cbc037e87827202e0bc21e8018fde2374d3d927da720279c1a11963ad63</citedby><cites>FETCH-LOGICAL-c385t-7dde67cbc037e87827202e0bc21e8018fde2374d3d927da720279c1a11963ad63</cites><orcidid>0000-0003-3203-3686</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,776,881,26544</link.rule.ids><linktorsrc>$$Uhttp://hdl.handle.net/10037/24422$$EView_record_in_NORA$$FView_record_in_$$GNORA$$Hfree_for_read</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33940655$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Frischmuth, Tobias</creatorcontrib><creatorcontrib>Hindberg, Kristian</creatorcontrib><creatorcontrib>Gabrielsen, Maiken E.</creatorcontrib><creatorcontrib>Brumpton, Ben</creatorcontrib><creatorcontrib>Hveem, Kristian</creatorcontrib><creatorcontrib>Brækkan, Sigrid K.</creatorcontrib><creatorcontrib>Hansen, John-Bjarne</creatorcontrib><creatorcontrib>Morelli, Vânia M.</creatorcontrib><title>Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Abstract
Background
The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear.
Objective
To investigate the joint effect of obesity and a genetic risk score (GRS) composed of established prothrombotic single nucleotide polymorphisms (SNPs) on VTE risk using a population-based case–cohort.
Methods
Cases with incident VTE (
n
= 1,470) and a subcohort (
n
= 12,826) were derived from the Tromsø Study (1994–2012) and the Trøndelag Health Study (HUNT) (1995–2008). Participants were genotyped for
ABO
(rs8176719),
F5
(rs6025),
F2
(rs1799963),
FGG
(rs2066865), and
F11
(rs2036914) SNPs. Age- and sex-adjusted hazard ratios (HRs) were estimated according to body mass index (BMI) categories and number of risk alleles for individual SNPs and the GRS (0–1, 2, 3, ≥4 alleles).
Results
The combination of obesity (BMI ≥ 30kg/m
2
) and risk alleles, either as individual SNPs or as a GRS, had an additive effect on VTE risk (i.e., no biological interaction). Obese subjects who were carriers of ≥4 risk alleles had a 2.85-fold (95% confidence interval [CI]: 2.05–3.96) increased risk of overall VTE compared with those with BMI <25 kg/m
2
and 0 to 1 risk allele. However, in subgroups, the combination of obesity and ≥4 risk alleles was more pronounced for deep vein thrombosis (DVT) (HR: 3.20; 95% CI: 2.09–4.90) and unprovoked VTE (HR: 3.82; 95% CI: 2.25–6.47), suggesting a supra-additive effect.
Conclusion
Our findings indicate that the combination of obesity and GRS has an additive effect on the risk of overall VTE. However, it may have a supra-additive effect on the risk of DVT and unprovoked VTE.</description><subject>Alleles</subject><subject>Female</subject><subject>Fibrinogen - genetics</subject><subject>Genotype</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Norway</subject><subject>Obesity - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prothrombin - genetics</subject><subject>Risk Factors</subject><subject>Stroke, Systemic or Venous Thromboembolism</subject><subject>Venous Thromboembolism - epidemiology</subject><subject>Venous Thromboembolism - genetics</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>3HK</sourceid><recordid>eNpt0D1PwzAQBmALgWgpTOzgGRTwRxInI6pKKSoqQgWxRYl9Ud0mcRU7Q_89jkKZGKwb_Nwr3YvQNSUPlETRYx7QMBVBKoQ4QWMWxSKIk_T7FI0JD0kQszAaoQtrt4TQOEyjczTiPA1JHEVjtHs1unF4VpYgHTYlfusqp_cV4PfWuE1r6sI4LfEcGuMOe7A4bxReFWC1O2DTYLcB_KHtrt9dNFIr8HFfXncWr4d98K_Str5EZ2VeWbj6nRP0-TxbT1-C5Wq-mD4tA8mTyAVCKYiFLCThAhKRMMEIA1JIRiEhNCkVMC5CxVXKhMr7X5FKmlOaxjxXMZ-g2yFXtto63WSNafOMEp-XsTBkzIv7ozDWtlBm-1bXeXvwKutLzbz3pWZ9qV7fDHrfFTWoP3ts0YO7AbiNhhqyrenaxl_4b9oPaEd-1Q</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Frischmuth, Tobias</creator><creator>Hindberg, Kristian</creator><creator>Gabrielsen, Maiken E.</creator><creator>Brumpton, Ben</creator><creator>Hveem, Kristian</creator><creator>Brækkan, Sigrid K.</creator><creator>Hansen, John-Bjarne</creator><creator>Morelli, Vânia M.</creator><general>Georg Thieme Verlag KG</general><general>Thieme Gruppe</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3HK</scope><orcidid>https://orcid.org/0000-0003-3203-3686</orcidid></search><sort><creationdate>20220201</creationdate><title>Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism</title><author>Frischmuth, Tobias ; Hindberg, Kristian ; Gabrielsen, Maiken E. ; Brumpton, Ben ; Hveem, Kristian ; Brækkan, Sigrid K. ; Hansen, John-Bjarne ; Morelli, Vânia M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-7dde67cbc037e87827202e0bc21e8018fde2374d3d927da720279c1a11963ad63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alleles</topic><topic>Female</topic><topic>Fibrinogen - genetics</topic><topic>Genotype</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Norway</topic><topic>Obesity - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prothrombin - genetics</topic><topic>Risk Factors</topic><topic>Stroke, Systemic or Venous Thromboembolism</topic><topic>Venous Thromboembolism - epidemiology</topic><topic>Venous Thromboembolism - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frischmuth, Tobias</creatorcontrib><creatorcontrib>Hindberg, Kristian</creatorcontrib><creatorcontrib>Gabrielsen, Maiken E.</creatorcontrib><creatorcontrib>Brumpton, Ben</creatorcontrib><creatorcontrib>Hveem, Kristian</creatorcontrib><creatorcontrib>Brækkan, Sigrid K.</creatorcontrib><creatorcontrib>Hansen, John-Bjarne</creatorcontrib><creatorcontrib>Morelli, Vânia M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>NORA - Norwegian Open Research Archives</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Frischmuth, Tobias</au><au>Hindberg, Kristian</au><au>Gabrielsen, Maiken E.</au><au>Brumpton, Ben</au><au>Hveem, Kristian</au><au>Brækkan, Sigrid K.</au><au>Hansen, John-Bjarne</au><au>Morelli, Vânia M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>122</volume><issue>2</issue><spage>267</spage><epage>276</epage><pages>267-276</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><abstract>Abstract
Background
The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear.
Objective
To investigate the joint effect of obesity and a genetic risk score (GRS) composed of established prothrombotic single nucleotide polymorphisms (SNPs) on VTE risk using a population-based case–cohort.
Methods
Cases with incident VTE (
n
= 1,470) and a subcohort (
n
= 12,826) were derived from the Tromsø Study (1994–2012) and the Trøndelag Health Study (HUNT) (1995–2008). Participants were genotyped for
ABO
(rs8176719),
F5
(rs6025),
F2
(rs1799963),
FGG
(rs2066865), and
F11
(rs2036914) SNPs. Age- and sex-adjusted hazard ratios (HRs) were estimated according to body mass index (BMI) categories and number of risk alleles for individual SNPs and the GRS (0–1, 2, 3, ≥4 alleles).
Results
The combination of obesity (BMI ≥ 30kg/m
2
) and risk alleles, either as individual SNPs or as a GRS, had an additive effect on VTE risk (i.e., no biological interaction). Obese subjects who were carriers of ≥4 risk alleles had a 2.85-fold (95% confidence interval [CI]: 2.05–3.96) increased risk of overall VTE compared with those with BMI <25 kg/m
2
and 0 to 1 risk allele. However, in subgroups, the combination of obesity and ≥4 risk alleles was more pronounced for deep vein thrombosis (DVT) (HR: 3.20; 95% CI: 2.09–4.90) and unprovoked VTE (HR: 3.82; 95% CI: 2.25–6.47), suggesting a supra-additive effect.
Conclusion
Our findings indicate that the combination of obesity and GRS has an additive effect on the risk of overall VTE. However, it may have a supra-additive effect on the risk of DVT and unprovoked VTE.</abstract><cop>Rüdigerstraße 14, 70469 Stuttgart, Germany</cop><pub>Georg Thieme Verlag KG</pub><pmid>33940655</pmid><doi>10.1055/a-1497-9777</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-3203-3686</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0340-6245 |
| ispartof | Thrombosis and haemostasis, 2022-02, Vol.122 (2), p.267-276 |
| issn | 0340-6245 2567-689X |
| language | eng |
| recordid | cdi_cristin_nora_10037_24422 |
| source | NORA - Norwegian Open Research Archives |
| subjects | Alleles Female Fibrinogen - genetics Genotype Humans Male Middle Aged Norway Obesity - genetics Polymorphism, Single Nucleotide Prothrombin - genetics Risk Factors Stroke, Systemic or Venous Thromboembolism Venous Thromboembolism - epidemiology Venous Thromboembolism - genetics |
| title | Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism |
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