Abstract
We performed a genomewide scan for genes that predispose to low serum HDL cholesterol (HDL-C) in 25 well-defined Finnish families that were ascertained for familial low HDL-C and premature coronary heart disease. The potential loci for low HDL-C that were identified initially were tested in an independent sample group of 29 Finnish families that were ascertained for familial combined hyperlipidemia (FCHL), expressing low HDL-C as one component trait. The data from the previous genome scan were also reanalyzed for this trait. We found evidence for linkage between the low-HDL-C trait and three loci, in a pooled data analysis of families with low HDL-C and FCHL. The strongest statistical evidence was obtained at a locus on chromosome 8q23, with a two-point LOD score of 4.7 under a recessive mode of inheritance and a multipoint LOD score of 3.3. Evidence for linkage also emerged for loci on chromosomes 16q24.1-24.2 and 20q13.11, the latter representing a recently characterized region for type 2 diabetes. Besides these three loci, loci on chromosomes 2p and 3p showed linkage in the families with low HDL-C and a locus on 2ptel in the families with FCHL.
MeSH Terms
Adult
Body Mass Index
Cholesterol, HDL/blood,genetics
Chromosome Mapping
Chromosomes, Human, Pair 16/genetics
Chromosomes, Human, Pair 2/genetics
Chromosomes, Human, Pair 20/genetics
Chromosomes, Human, Pair 3/genetics
Chromosomes, Human, Pair 8/genetics
Diabetes Mellitus, Type 2/genetics
Female
Finland
Genes, Recessive/genetics
Genome, Human
Humans
Lod Score
Male
Middle Aged
Phenotype
Chemicals
Cholesterol, HDL
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Soro Aino
Department of Human Genetics, Gonda Neuroscience and Genetics Research Center, University of California, Los Angeles, CA 90095-7088, USA.
Pajukanta Päivi
Lilja Heidi E
Ylitalo Kati
Hiekkalinna Tero
Perola Markus
Cantor Rita M
Viikari Jorma S A
Taskinen Marja-Riitta
Peltonen Leena
References (26)
26 references, click to expand
-
Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics.
Am J Hum Genet. 1996 Jun;58(6):1323-37
PMID: 8651310
-
Age and gender specific serum lipid and apolipoprotein fractiles of Finnish children and young adults. The Cardiovascular Risk in Young Finns Study.
Acta Paediatr. 1994 Aug;83(8):838-48
PMID: 7981561
-
Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy.
Diabetes. 1997 May;46(5):882-6
PMID: 9133559
-
Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q.
J Clin Invest. 1997 Sep 1;100(5):1240-7
PMID: 9276742
-
Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23.
Nat Genet. 1998 Apr;18(4):369-73
PMID: 9537421
-
Multipoint quantitative-trait linkage analysis in general pedigrees.
Am J Hum Genet. 1998 May;62(5):1198-211
PMID: 9545414
-
PedCheck: a program for identification of genotype incompatibilities in linkage analysis.
Am J Hum Genet. 1998 Jul;63(1):259-66
PMID: 9634505
-
Genetics of lipoprotein disorders.
Endocrinol Metab Clin North Am. 1998 Sep;27(3):521-50
PMID: 9785051
-
Genomewide scan for familial combined hyperlipidemia genes in finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels.
Am J Hum Genet. 1999 May;64(5):1453-63
PMID: 10205279
-
Human pedigree-based quantitative-trait-locus mapping: localization of two genes influencing HDL-cholesterol metabolism.
Am J Hum Genet. 1999 Jun;64(6):1686-93
PMID: 10330356
-
A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11.
Am J Hum Genet. 1999 Aug;65(2):397-412
PMID: 10417282
-
Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.
Nat Genet. 1999 Aug;22(4):336-45
PMID: 10431236
-
Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1.
Nat Genet. 1999 Aug;22(4):352-5
PMID: 10431238
-
Molecular genetics of the Finnish disease heritage.
Hum Mol Genet. 1999;8(10):1913-23
PMID: 10469845
-
Gene mapping in the 20th and 21st centuries: statistical methods, data analysis, and experimental design.
Hum Biol. 2000 Feb;72(1):63-132
PMID: 10721614
-
Linkage analysis in the presence of errors III: marker loci and their map as nuisance parameters.
Am J Hum Genet. 2000 Apr;66(4):1298-309
PMID: 10731467
-
The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to type 2 diabetes.
Am J Hum Genet. 2000 Nov;67(5):1174-85
PMID: 11032783
-
Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease.
Circulation. 2001 Mar 6;103(9):1198-205
PMID: 11238261
-
A candidate gene study in low HDL-cholesterol families provides evidence for the involvement of the APOA2 gene and the APOA1C3A4 gene cluster.
Atherosclerosis. 2002 Sep;164(1):103-11
PMID: 12119199
-
Strategies for multilocus linkage analysis in humans.
Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443-6
PMID: 6587361
-
Familial lipoprotein disorders in patients with premature coronary artery disease.
Circulation. 1992 Jun;85(6):2025-33
PMID: 1534286
-
A haplotype-based 'haplotype relative risk' approach to detecting allelic associations.
Hum Hered. 1992;42(6):337-46
PMID: 1493912
-
Faster sequential genetic linkage computations.
Am J Hum Genet. 1993 Jul;53(1):252-63
PMID: 8317490
-
Avoiding recomputation in linkage analysis.
Hum Hered. 1994 Jul-Aug;44(4):225-37
PMID: 8056435
-
Twenty-year trends in coronary risk factors in north Karelia and in other areas of Finland.
Int J Epidemiol. 1994 Jun;23(3):495-504
PMID: 7960373
-
A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2.
Nat Genet. 1996 Aug;13(4):477-80
PMID: 8696346