Abstract:
:Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in the LpL gene. LDL particle size was smaller among the heterozygous subjects, compared with controls. Among heterozygous subjects, 44% were classified as affected by LDL subclass phenotype B, compared with 8% of normal family members. Plasma triglyceride levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in heterozygous subjects, compared with normal subjects, after age and sex adjustment. A highly significant LOD score of 6.24 at straight theta=0 was obtained for linkage of LDL particle size to the LpL gene, after adjustment of LDL particle size for within-genotype variance resulting from triglyceride and HDL-C. Failure to adjust for this variance led to only a modest positive LOD score of 1.54 at straight theta=0. Classifying small LDL particles as a qualitative trait (LDL subclass phenotype B) provided only suggestive evidence for linkage to the LpL gene (LOD=1. 65 at straight theta=0). Thus, use of the quantitative trait adjusted for within-genotype variance, resulting from physiologic covariates, was crucial for detection of significant evidence of linkage in this study. These results indicate that heterozygous LpL deficiency may be one cause of small LDL particles and may provide a potential mechanism for the increase in coronary disease seen in heterozygous LpL deficiency. This study also demonstrates a successful strategy of genotypic specific adjustment of complex traits in mapping a quantitative trait locus.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Hokanson JE,Brunzell JD,Jarvik GP,Wijsman EM,Austin MAdoi
10.1086/302234subject
Has Abstractpub_date
1999-02-01 00:00:00pages
608-18issue
2eissn
0002-9297issn
1537-6605pii
S0002-9297(07)61768-6journal_volume
64pub_type
杂志文章abstract::A current approach to mapping complex-disease-susceptibility loci in genome-wide association (GWA) studies involves leveraging the information in a reference database of dense genotype data. By modeling the patterns of linkage disequilibrium in a reference panel, genotypes not directly measured in the study samples ca...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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更新日期:1996-04-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
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journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:1994-11-01 00:00:00
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journal_title:American journal of human genetics
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更新日期:1995-10-01 00:00:00
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journal_title:American journal of human genetics
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更新日期:1997-05-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.06.005
更新日期:2012-08-10 00:00:00
abstract::Although Africa has played a central role in human evolutionary history, certain studies have suggested that not all contemporary human genetic diversity is of recent African origin. We investigated 35 simple polymorphic sites and one T(n) microsatellite in an 8-kb segment of the dystrophin gene. We found 86 haplotype...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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doi:
更新日期:1994-05-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
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abstract::Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.10.002
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journal_title:American journal of human genetics
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更新日期:1988-06-01 00:00:00
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journal_title:American journal of human genetics
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doi:10.1016/j.ajhg.2010.04.010
更新日期:2010-06-11 00:00:00
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journal_title:American journal of human genetics
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更新日期:1983-05-01 00:00:00
abstract::Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by waxing and waning multiple motor and phonic tics with a complex mode of inheritance. Previous attempts, which used large multigenerational families to localize susceptibility loci, have been unsuccessful. In this report, the results of the ...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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更新日期:1996-04-01 00:00:00