TY - JOUR
T1 - A cholesterol-lowering gene maps to chromosome 13q
AU - Knoblauch, Hans
AU - Müller-Myhsok, Bertram
AU - Busjahn, Andreas
AU - Avi, Liat Ben
AU - Bähring, Sylvia
AU - Baron, Heike
AU - Heath, Simon C.
AU - Uhlmann, Regina
AU - Faulhaber, Hans Dieter
AU - Shpitzen, Shoshi
AU - Aydin, Atakan
AU - Reshef, Ayeleth
AU - Rosenthal, Magda
AU - Eliav, Osnat
AU - Mühl, Astrid
AU - Lowe, Adam
AU - Schurr, Danny
AU - Harats, Dror
AU - Jeschke, Evi
AU - Friedlander, Yechiel
AU - Schuster, Herbert
AU - Luft, Friedrich C.
AU - Leitersdorf, Eran
PY - 2000
Y1 - 2000
N2 - A cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158. FASTLINK and GENE-HUNTER yielded LOD scores > 5 and > 4, respectively, whereas an affected-sib-pair analysis gave a peak multipoint LOD score of 4.8, corresponding to a P value of 1.26 x 10-6. A multipoint quantitative-trait-locus (QTL) linkage analysis with maximum-likelihood binomial QTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied MZ and DZ twin subjects. An MZ-DZ comparison confirmed genetic variance with regard to lipid concentrations. We then performed an identity-by-descent linkage analysis on the DZ twins, with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (P < .0002), HDL (P < .004), total cholesterol (P < .0002), and body-mass index (P < .0001). These data provide support for the existence of a new gene influencing lipid concentrations in humans.
AB - A cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158. FASTLINK and GENE-HUNTER yielded LOD scores > 5 and > 4, respectively, whereas an affected-sib-pair analysis gave a peak multipoint LOD score of 4.8, corresponding to a P value of 1.26 x 10-6. A multipoint quantitative-trait-locus (QTL) linkage analysis with maximum-likelihood binomial QTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied MZ and DZ twin subjects. An MZ-DZ comparison confirmed genetic variance with regard to lipid concentrations. We then performed an identity-by-descent linkage analysis on the DZ twins, with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (P < .0002), HDL (P < .004), total cholesterol (P < .0002), and body-mass index (P < .0001). These data provide support for the existence of a new gene influencing lipid concentrations in humans.
UR - http://www.scopus.com/inward/record.url?scp=0033925280&partnerID=8YFLogxK
U2 - 10.1086/302704
DO - 10.1086/302704
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C2 - 10631147
AN - SCOPUS:0033925280
SN - 0002-9297
VL - 66
SP - 157
EP - 166
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -