Combined association and linkage analysis applied to the APOE locus
Open accessAbstract
Combined association and linkage analysis is a powerful tool for pinpointing functional quantitative traits (QTLs) responsible for regions of significant linkage identified in genome‐wide scans. We applied this technique to apoE plasma levels and the APOEε2/ε3/ε4 polymorphism in two Dutch twin cohorts of different age ranges. Across chromosome 19, short tandem repeats and the APOEε2/ε3/ε4 polymorphism were genotyped in adolescent (aged 13–22 years) and adult (aged 34–62 years) Dutch twins. In both samples, evidence for indicative linkage with plasma apoE levels was found (maximum LOD score (MLS)=0.8, MLS=2.5, respectively) at 19q13.32. These linkage regions included the APOE locus. As expected, the APOEε2/ε3/ε4 polymorphism was strongly associated with apoE plasma levels in both samples. An extension of the between/within families association test developed by Fulker et al. ([1999] Am. J. Hum. Genet. 64:259–267) showed that these associations were not due to population stratification. The combined association and linkage analyses revealed that the association of the APOEε2/ε3/ε4 polymorphism with apoE plasma levels completely explained the linkage in the adolescent twins and partly in the adult twins. © 2004 Wiley‐Liss, Inc.
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The APOE ɛ2/ɛ3/ɛ4 genotype is only a minor determinant of plasma apoE levels.
“the APOE ɛ2/ɛ3/ɛ4 genotype is only a minor determinant of these levels [ 8, 40]”
From ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age (2006) · cites this paper as [40]
The indexed Abstract reports that the APOE ε2/ε3/ε4 polymorphism was strongly associated with plasma apoE levels in two Dutch twin cohorts. It does not establish that the genotype is only a minor determinant of those levels; strength of association alone does not quantify its contribution to variation in levels. (LLM, conf=0.78)
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Quality and trustworthiness in qualitative research in counseling psychology.
Morrow, S. L. (2005) · Journal of Counseling Psychology · doi:10.1037/0022-0167.52.2.250 · Cited by 3,199 · see citing works
Sahlins, M., & Graeber, D. (2017) · Routledge (orig. 1972) · doi:10.4324/9781315184951 · Cited by 3,159 · see citing works
A General Test of Association for Quantitative Traits in Nuclear Families
Abecasis, G. R., Cardon, L. R., & Cookson, W. O. C. (2000) · The American Journal of Human Genetics · doi:10.1086/302698 · Cited by 1,126 · see citing works
Allelic polymorphisms in the transcriptional regulatory region of apolipoprotein E gene
Artiga, M. J., Bullido, M. J., Sastre, I., Recuero, M., Garcı́a, M. A., Aldudo, J., Vázquez, J., & Valdivieso, F. (1998) · FEBS Letters · doi:10.1016/s0014-5793(97)01543-3 · Cited by 229 · see citing works
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ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age
Mooijaart, S. P., Berbée, J. F. P., van Heemst, D., Havekes, L. M., de Craen, A. J. M., Slagboom, P. E., Rensen, P. C. N., & Westendorp, R. G. J. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030176 · Cited by 129 · see citing works
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- Authors
- Beekman, M., Posthuma, D., Heijmans, B. T., Lakenberg, N., Suchiman, H. E. D., Snieder, H., de Knijff, P., Frants, R. R., van Ommen, G. J. B., Kluft, C., Vogler, G. P., Slagboom, P. E., & Boomsma, D. I.
- Affiliations
- Leiden University Medical Center (NL)
- St Thomas' Hospital (GB)
- Netherlands Organisation for Applied Scientific Research (NL)
- Pennsylvania State University (US)
- Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Beekman, Marian
- ORCID
- Venue
- Genetic Epidemiology
- Publisher
- Wiley
- Published
- 2004-02-25
- Volume
- 26
- Issue
- 4
- Pages
- 328-337
- ISSN
- 0741-0395 (ISSN-L)
- 1098-2272
- OpenAlex
- W1986764755
- Cited by
- 16
- References
- 4
- Citations by year
- 2025: 2 · 2024: 1 · 2020: 1 · 2013: 2 · 2012: 1
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- green
- research.vu.nl
- Licence
- Locations
- Genetic Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- TNO Repository (submittedVersion)
- Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-55976, R01HL055976)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- quantitative trait loci, linkage analysis, association analysis, twin cohort, microsatellite markers, population stratification
- MeSH terms
- Adolescent, Adult, Apolipoproteins E, Chromosomes, Human, Pair 19, Female, Genotype, Humans, Genetic Linkage, Lod Score, Male, Netherlands, Polymorphism, Genetic, Cohort Studies, Quantitative Trait, Heritable, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
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