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.
Baumert J., Huang J., McKnight B., Sabater-Lleal M., Steri M., Chu AY., Trompet S., Lopez LM., Fornage M., Teumer A., Tang W., Rudnicka AR., Mälarstig A., Hottenga JJ., Kavousi M., Lahti J., Tanaka T., Hayward C., Huffman JE., Morange PE., Rose LM., Basu S., Rumley A., Stott DJ., Buckley BM., de Craen AJ., Sanna S., Masala M., Biffar R., Homuth G., Silveira A., Sennblad B., Goel A., Watkins H., Müller-Nurasyid M., Rückerl R., Taylor K., Chen MH., de Geus EJ., Hofman A., Witteman JC., de Maat MP., Palotie A., Davies G., Siscovick DS., Kolcic I., Wild SH., Song J., McArdle WL., Ford I., Sattar N., Schlessinger D., Grotevendt A., Franzosi MG., Illig T., Waldenberger M., Lumley T., Tofler GH., Willemsen G., Uitterlinden AG., Rivadeneira F., Räikkönen K., Chasman DI., Folsom AR., Lowe GD., Westendorp RG., Slagboom PE., Cucca F., Wallaschofski H., Strawbridge RJ., Seedorf U., Koenig W., Bis JC., Mukamal KJ., van Dongen J., Widen E., Franco OH., Starr JM., Liu K., Ferrucci L., Polasek O., Wilson JF., Oudot-Mellakh T., Campbell H., Navarro P., Bandinelli S., Eriksson J., Boomsma DI., Dehghan A., Clarke R., Hamsten A., Boerwinkle E., Jukema JW., Naitza S., Ridker PM., Völzke H., Deary IJ., Reiner AP., Trégouët DA., O'Donnell CJ., Strachan DP., Peters A., Smith NL.
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 6.2 × 10(-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.