No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects

被引：6

作者：

Baumert, Jens ^{[1
]}

Huang, Jie ^{[2
,3
,4
]}

McKnight, Barbara ^{[5
]}

Sabater-Lleal, Maria ^{[6
]}

Steri, Maristella ^{[7
]}

Chu, Audrey Y. ^{[8
]}

Trompet, Stella ^{[9
,10
]}

Lopez, Lorna M. ^{[11
,12
]}

Fornage, Myriam ^{[13
]}

Teumer, Alexander ^{[14
]}

Tang, Weihong ^{[15
]}

Rudnicka, Alicja R. ^{[16
]}

Maelarstig, Anders ^{[6
]}

Hottenga, Jouke-Jan ^{[17
,18
]}

Kavousi, Maryam ^{[19
,20
]}

Lahti, Jari ^{[21
,22
]}

Tanaka, Toshiko ^{[23
]}

Hayward, Caroline ^{[24
]}

Huffman, Jennifer E. ^{[24
]}

Morange, Pierre-Emmanuel ^{[25
]}

Rose, Lynda M. ^{[8
]}

Basu, Saonli ^{[26
]}

Rumley, Ann ^{[27
]}

Stott, David J. ^{[28
]}

Buckley, Brendan M. ^{[29
]}

de Craen, Anton J. M. ^{[10
]}

Sanna, Serena ^{[7
]}

Masala, Marco ^{[7
]}

Biffar, Reiner ^{[30
]}

Homuth, Georg ^{[14
]}

Silveira, Angela ^{[6
]}

Sennblad, Bengt ^{[6
,31
]}

Goel, Anuj ^{[32
,33
]}

Watkins, Hugh ^{[32
,33
]}

Mueller-Nurasyid, Martina ^{[34
,35
,36
]}

Rueckerl, Regina ^{[1
,37
]}

Taylor, Kent ^{[38
]}

Chen, Ming-Huei ^{[39
]}

de Geus, Eco J. C. ^{[40
]}

Hofman, Albert ^{[19
,20
]}

Witteman, Jacqueline C. M. ^{[19
,20
]}

de Maat, Moniek P. M. ^{[40
]}

Palotie, Aarno ^{[41
,42
,43
,44
]}

Davies, Gail ^{[11
,12
]}

Siscovick, David S. ^{[45
]}

Kolcic, Ivana ^{[46
]}

Wild, Sarah H. ^{[47
]}

Song, Jaejoon ^{[26
]}

McArdle, Wendy L. ^{[48
]}

Ford, Ian ^{[49
]}

机构：

[1] Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, Neuherberg, Germany

[2] NHLBI, Framingham Heart Study, Framingham, MA USA

[3] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA

[4] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England

[5] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[6] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med, Cardiovasc Genet & Genom Grp,Atherosclerosis Res, Stockholm, Sweden

[7] CNR, Ist Ric Genet & Biomed, Cagliari, Italy

[8] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

[9] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands

[10] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands

[11] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland

[12] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[13] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Div Epidemiol, Sch Publ Hlth, Houston, TX 77030 USA

[14] Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[15] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[16] Univ London, Div Populat Hlth Sci & Educ, London, England

[17] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[18] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands

[19] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[20] NCHA, NGI, Rotterdam, Netherlands

[21] Univ Helsinki, Inst Behav Sci, Helsinki, Finland

[22] Folkhalsan Res Ctr, Helsinki, Finland

[23] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA

[24] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland

[25] Aix Marseille Univ, INSERM, UMR S 1062, Marseille, France

[26] Univ Minnesota, Div Biostat, Minneapolis, MN USA

[27] Univ Glasgow, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[28] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[29] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland

[30] Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany

[31] Karolinska Inst, Sci Life Lab, Stockholm, Sweden

[32] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England

[33] Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford, England

[34] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany

[35] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany

[36] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany

[37] Univ Augsburg, ESC Environm Sci Ctr, D-86159 Augsburg, Germany

[38] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[39] Boston Univ, Dept Biostat, Boston, MA 02215 USA

[40] Erasmus MC, Dept Haematol, Rotterdam, Netherlands

[41] Wellcome Trust Sanger Inst, Cambridge, England

[42] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[43] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[44] Univ Cent Hosp, Helsinki, Finland

[45] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[46] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia

[47] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland

[48] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[49] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland

[50] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland

来源：

PLOS ONE | 2014年 / 9卷 / 12期

关键词：

CARDIOVASCULAR RISK-FACTORS; CIRCULATING FIBRINOGEN; MYOCARDIAL-INFARCTION; INFLAMMATORY MARKERS; CIGARETTE-SMOKING; GENETIC-VARIATION; ASSOCIATION; DISEASE; LOCI; CANCER;

D O I：

10.1371/journal.pone.0111156

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2x10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

引用

页数：18

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