TY - JOUR
T1 - A genome-wide linkage scan for homocysteine levels suggests three regions of interest
AU - Vermeulen, S. H.H.M.
AU - Van Der Vleuten, G. M.
AU - De Graaf, J.
AU - Hermus, A. R.
AU - Blom, H. J.
AU - Stalenhoef, A. F.H.
AU - Den Heijer, M.
PY - 2006/6
Y1 - 2006/6
N2 - Background: An elevated plasma total homocysteine (tHcy) level is a risk factor for many clinical conditions, including vascular disease and venous thrombosis. The tHcy levels are partly determined by genetic factors. Extensive candidate gene studies have identified several genetic variants, including the MTHFR 677C>T, that influence tHcy levels, but so far only part of the genetic variation in tHcy can be explained. Objective: In order to identify chromosomal regions that influence tHcy levels, a genome-wide linkage analysis was conducted. Patients/methods: Our study population consisted of 13 pedigrees and 469 subjects with data on fasting plasma tHcy levels. A set of 377 markers covering the genome was genotyped in 275 subjects. The variance component linkage method (SOLAR version 2.1.3) was used for the two-point and multipoint linkage analyses. Results: The heritability of the age- and sexadjusted homocysteine levels was 44%. The multipoint linkage analysis identified one region with suggestive linkage on chromosome 16q (LOD score 1.76; nominal P = 0.0024). Weaker evidence of linkage was found for regions on chromosome 12q (LOD score 1.57; nominal P = 0.0036) and chromosome 13q (LOD score 1.52; nominal P = 0.0041). Conclusions: In our families the plasma tHcy level was highly heritable. The multipoint linkage analysis identified three regions that showed weak to suggestive linkage to tHcy levels.
AB - Background: An elevated plasma total homocysteine (tHcy) level is a risk factor for many clinical conditions, including vascular disease and venous thrombosis. The tHcy levels are partly determined by genetic factors. Extensive candidate gene studies have identified several genetic variants, including the MTHFR 677C>T, that influence tHcy levels, but so far only part of the genetic variation in tHcy can be explained. Objective: In order to identify chromosomal regions that influence tHcy levels, a genome-wide linkage analysis was conducted. Patients/methods: Our study population consisted of 13 pedigrees and 469 subjects with data on fasting plasma tHcy levels. A set of 377 markers covering the genome was genotyped in 275 subjects. The variance component linkage method (SOLAR version 2.1.3) was used for the two-point and multipoint linkage analyses. Results: The heritability of the age- and sexadjusted homocysteine levels was 44%. The multipoint linkage analysis identified one region with suggestive linkage on chromosome 16q (LOD score 1.76; nominal P = 0.0024). Weaker evidence of linkage was found for regions on chromosome 12q (LOD score 1.57; nominal P = 0.0036) and chromosome 13q (LOD score 1.52; nominal P = 0.0041). Conclusions: In our families the plasma tHcy level was highly heritable. The multipoint linkage analysis identified three regions that showed weak to suggestive linkage to tHcy levels.
KW - Genome-wide linkage scan
KW - Homocysteine
KW - Quantitative trait locus
KW - Variance components linkage analysis
UR - http://www.scopus.com/inward/record.url?scp=33646765367&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/j.1538-7836.2006.01977.x
DO - https://doi.org/10.1111/j.1538-7836.2006.01977.x
M3 - Article
C2 - 16706975
SN - 1538-7933
VL - 4
SP - 1303
EP - 1307
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 6
ER -