TY - JOUR
T1 - 2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio
AU - Lin, Bochao Danae
AU - Carnero-Montoro, Elena
AU - Bell, Jordana T.
AU - Boomsma, Dorret I.
AU - de Geus, Eco J.
AU - Jansen, Rick
AU - Kluft, Cornelis
AU - Mangino, Massimo
AU - Penninx, Brenda
AU - Spector, Tim D.
AU - Willemsen, Gonneke
AU - Hottenga, Jouke-Jan
PY - 2017/11
Y1 - 2017/11
N2 - Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and estimated SNP heritability in a sample of 5901 related healthy Dutch individuals. GWA analyses identified a new genome-wide significant locus on the HBS1L-MYB intergenic region for PLR, which replicated in a sample of 2538 British twins. For platelet count, we replicated three known genome-wide significant loci in our cohort (at CCDC71L-PIK3CG, BAK1 and ARHGEF3). For neutrophil count, we replicated the PSMD3 locus. For the identified top SNPs, we found significant cis and trans expression quantitative trait loci effects for several loci involved in hematological and immunological pathways. Linkage Disequilibrium score (LD) regression analyses for PLR and NLR confirmed that both traits are heritable, with a polygenetic SNP heritability for PLR of 14.1%, and for NLR of 2.4%. Genetic correlations were present between ratios and the constituent counts, with the genetic correlation (r=0.45) of PLR with platelet count reaching statistical significance. In conclusion, we established that two important biomarkers have a significant heritable SNP component, and identified the first genome-wide locus for PLR.
AB - Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and estimated SNP heritability in a sample of 5901 related healthy Dutch individuals. GWA analyses identified a new genome-wide significant locus on the HBS1L-MYB intergenic region for PLR, which replicated in a sample of 2538 British twins. For platelet count, we replicated three known genome-wide significant loci in our cohort (at CCDC71L-PIK3CG, BAK1 and ARHGEF3). For neutrophil count, we replicated the PSMD3 locus. For the identified top SNPs, we found significant cis and trans expression quantitative trait loci effects for several loci involved in hematological and immunological pathways. Linkage Disequilibrium score (LD) regression analyses for PLR and NLR confirmed that both traits are heritable, with a polygenetic SNP heritability for PLR of 14.1%, and for NLR of 2.4%. Genetic correlations were present between ratios and the constituent counts, with the genetic correlation (r=0.45) of PLR with platelet count reaching statistical significance. In conclusion, we established that two important biomarkers have a significant heritable SNP component, and identified the first genome-wide locus for PLR.
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?scp=85042726109&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042726109&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/jhg.2017.76
DO - https://doi.org/10.1038/jhg.2017.76
M3 - Article
C2 - 29066854
SN - 1434-5161
VL - 62
SP - 979
EP - 988
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 11
ER -