TY - JOUR
T1 - Linkage and Association Analysis Identifies TRAF1 Influencing Common Carotid Intima-Media Thickness
AU - Heßler, Nicole
AU - Geisel, Marie Henrike
AU - Coassin, Stefan
AU - Erbel, Raimund
AU - Heilmann, Stefanie
AU - Hennig, Frauke
AU - Hoffmann, Barbara
AU - Jöckel, Karl Heinz
AU - Moebus, Susanne
AU - Moskau-Hartmann, Susanna
AU - Nürnberg, Gudrun
AU - Nürnberg, Peter
AU - Vens, Maren
AU - Klockgether, Thomas
AU - Kronenberg, Florian
AU - Scherag, André
AU - Ziegler, Andreas
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background and Purpose - Carotid intima-media thickness is a marker for subclinical atherosclerosis that predicts subsequent clinical cardiovascular events. The aim of this study was to identify chromosomal loci with linkage or association to common carotid intima-media thickness. Methods - Nuclear families were recruited using the single parental proband sib-pair design. Genotype data were available for 546 individuals from 132 nuclear families of the Bonn IMT Family Study using the Affymetrix GeneChip Human Mapping 250K Sty chip. Multipoint logarithm of the odds (LOD) scores were determined with the quantitative trait locus statistic implemented in multipoint engine for rapid likelihood. Linkage analysis and family-based association tests were conducted. Data from 2471 German participants from the HNR (Heinz Nixdorf Recall) Study were used for subsequent replication. Results - Two new genomic regions with suggestive linkage (LOD>2) were identified on chromosome 4 (LOD=2.26) and on chromosome 17 (LOD=2.01). Previously reported linkage findings were replicated on chromosomes 13 and 14. Fifteen single nucleotide polymorhisms, located on chromosomes 4, 6, and 9, revealed P<10 -4 in the family-based association analyses. One of these signals was replicated in HNR (rs2416804, 1-sided P=1.60×10 -3, located in the gene TRAF1). Conclusions - This study presents the first genome-wide linkage and association study of common carotid intima-media thickness in the German population. Alleles of rs2416804 in TRAF1 were identified as being linked and associated with carotid intima-media thickness. Further studies are needed to evaluate the contribution of this locus to the development of atherosclerosis.
AB - Background and Purpose - Carotid intima-media thickness is a marker for subclinical atherosclerosis that predicts subsequent clinical cardiovascular events. The aim of this study was to identify chromosomal loci with linkage or association to common carotid intima-media thickness. Methods - Nuclear families were recruited using the single parental proband sib-pair design. Genotype data were available for 546 individuals from 132 nuclear families of the Bonn IMT Family Study using the Affymetrix GeneChip Human Mapping 250K Sty chip. Multipoint logarithm of the odds (LOD) scores were determined with the quantitative trait locus statistic implemented in multipoint engine for rapid likelihood. Linkage analysis and family-based association tests were conducted. Data from 2471 German participants from the HNR (Heinz Nixdorf Recall) Study were used for subsequent replication. Results - Two new genomic regions with suggestive linkage (LOD>2) were identified on chromosome 4 (LOD=2.26) and on chromosome 17 (LOD=2.01). Previously reported linkage findings were replicated on chromosomes 13 and 14. Fifteen single nucleotide polymorhisms, located on chromosomes 4, 6, and 9, revealed P<10 -4 in the family-based association analyses. One of these signals was replicated in HNR (rs2416804, 1-sided P=1.60×10 -3, located in the gene TRAF1). Conclusions - This study presents the first genome-wide linkage and association study of common carotid intima-media thickness in the German population. Alleles of rs2416804 in TRAF1 were identified as being linked and associated with carotid intima-media thickness. Further studies are needed to evaluate the contribution of this locus to the development of atherosclerosis.
UR - http://www.scopus.com/inward/record.url?scp=84994682198&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.116.013943
DO - 10.1161/STROKEAHA.116.013943
M3 - Journal articles
C2 - 27827325
AN - SCOPUS:84994682198
SN - 0039-2499
VL - 47
SP - 2904
EP - 2909
JO - Stroke
JF - Stroke
IS - 12
ER -
