Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid and lipoprotein levels in the Quebec Family Study

被引:56
作者
Bossé, Y
Chagnon, YC
Després, CJP
Rice, T
Rao, DC
Bouchard, C
Pérusse, L
Vohl, MC [1 ]
机构
[1] Univ Laval, Med Res Ctr, Lipid Res Ctr, Quebec City, PQ, Canada
[2] Univ Laval, Dept Food Sci & Nutr, Quebec City, PQ, Canada
[3] Univ Laval, Robert Giffard Res Ctr, Beauport, PQ, Canada
[4] Quebec Heart Inst, Quebec City, PQ, Canada
[5] Univ Washington, Sch Med, Div Biostat, Seattle, WA 98195 USA
[6] Pennington Biomed Res Ctr, Baton Rouge, LA USA
[7] Univ Laval, Dept Social & Prevent Med, Quebec City, PQ, Canada
[8] Univ Laval, Div Kinesiol, Quebec City, PQ, Canada
关键词
genome scan; genetics; blood lipids; quantitative trait locus; triglyceride; cholesterol;
D O I
10.1194/jlr.M300401-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A genome-wide linkage study was performed to identify chromosomal regions harboring genes influencing lipid and lipoprotein levels. Linkage analyses were conducted for four quantitative lipoprotein/lipid traits, i.e., total cholesterol, triglyceride, HDL-cholesterol (HDL-C), and LDL-C concentrations, in 930 subjects enrolled in the Quebec Family Study. A maximum of 534 pairs of siblings from 292 nuclear families were available. Linkage was tested using both allele-sharing and variance-component linkage methods. The strongest evidence of linkage was found on chromosome 12q14.1 at marker D12S334 for HDL-C, with a logarithm of the odds (LOD) score of 4.06. Chromosomal regions harboring quantitative trait loci (QTLs) for LDL-C included 1q43 (LOD = 2.50), 11q23.2 (LOD = 3.22),15q26.1 (LOD = 3.11), and 19q13.32 (LOD = 3.59). In the case of triglycerides, three markers located on 2p14, 11p13, and 11q24.1 provided suggestive evidence of linkage (LOD > 1.75). Tests for total cholesterol levels yielded significant evidence of linkage at 15q26.1 and 18q22.3 with the allele-sharing linkage method, but the results were nonsignificant with the variance-component method. In conclusion, this genome scan provides evidence for several QTLs influencing lipid and lipoprotein levels. Promising candidate genes were located in the vicinity of the genomic regions showing evidence of linkage.-Bosse, Y, Y C. Chagnon, J-P. Despres, T. Rice, D. C. Rao, C. Bouchard, L. Perusse, and M-C. Vohl. Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid and lipoprotein levels in the Quebec Family Study.
引用
收藏
页码:419 / 426
页数:8
相关论文
共 44 条
[31]   The genetic dissection of complex traits in a founder population [J].
Ober, C ;
Abney, M ;
McPeek, MS .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (05) :1068-1079
[32]   Genomewide scan for familial combined hyperlipidemia genes in Finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels [J].
Pajukanta, P ;
Terwilliger, JD ;
Perola, M ;
Hiekkalinna, T ;
Nuotio, I ;
Ellonen, P ;
Parkkonen, M ;
Hartiala, J ;
Ylitalo, K ;
Pihlajamäki, J ;
Porkka, K ;
Laakso, M ;
Viikari, J ;
Ehnholm, C ;
Taskinen, MR ;
Peltonen, L .
AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (05) :1453-1463
[33]   Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23 [J].
Pajukanta, P ;
Nuotio, I ;
Terwilliger, JD ;
Porkka, KVK ;
Ylitalo, K ;
Pihlajamäki, J ;
Suomalainen, AJ ;
Syvänen, AC ;
Lehtimäki, T ;
Viikari, JSA ;
Laakso, M ;
Taskinen, MR ;
Ehnholm, C ;
Peltonen, L .
NATURE GENETICS, 1998, 18 (04) :369-373
[34]   Combined analysis of genome scans of Dutch and Finnish families reveals a susceptibility locus for high-density lipoprotein cholesterol on chromosome 16q [J].
Pajukanta, P ;
Allayee, H ;
Krass, KL ;
Kuraishy, A ;
Soro, A ;
Lilja, HE ;
Mar, R ;
Taskinen, MR ;
Nuotio, I ;
Laakso, M ;
Rotter, JI ;
de Bruin, TWA ;
Cantor, RM ;
Lusis, AJ ;
Peltonen, L .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (04) :903-917
[35]   Genome scan for quantitative trait loci linked to high-density lipoprotein cholesterol - The NHLBI family heart study [J].
Peacock, JM ;
Arnett, DK ;
Atwood, LD ;
Myers, RH ;
Coon, H ;
Rich, SS ;
Province, MA ;
Heiss, G .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2001, 21 (11) :1823-1828
[36]   Support for linkage of familial combined hyperlipidemia to chromosome 1q21-q23 in Chinese and German families [J].
Pei, WD ;
Baron, H ;
Müller-Myhsok, B ;
Knoblauch, H ;
Al-Yahyaee, SA ;
Hui, RT ;
Wu, XG ;
Liu, LS ;
Busjahn, A ;
Luft, FC ;
Schuster, H .
CLINICAL GENETICS, 2000, 57 (01) :29-34
[37]   Sequential methods of analysis for genome scans [J].
Province, MA .
GENETIC DISSECTION OF COMPLEX TRAITS, 2001, 42 :499-514
[38]   A genome search identifies major quantitative trait loci on human chromosomes 3 and 4 that influence cholesterol concentrations in small LDL particles [J].
Rainwater, DL ;
Almasy, L ;
Blangero, J ;
Cole, SA ;
VandeBerg, JL ;
MacCluer, JW ;
Hixson, JE .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (03) :777-783
[39]   The future of path analysis, segregation analysis, and combined models for genetic dissection of complex traits [J].
Rao, DC ;
Province, MA .
HUMAN HEREDITY, 2000, 50 (01) :34-42
[40]   A genome-wide scan suggests a locus on chromosome 1q21-q23 contributes to normal variation in plasma cholesterol concentration [J].
Reed, DR ;
Nanthakumar, E ;
North, M ;
Bell, C ;
Price, RA .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2001, 79 (5-6) :262-269