Title
Combined Association and Linkage Analysis Applied to the APOE Locus
Author
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.
Publication year
2004
Abstract
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. Chemicals / CAS: Apolipoprotein E2; Apolipoprotein E3; Apolipoprotein E4; Apolipoproteins E
Subject
ApoE level
Fine-mapping
Quantitative trait locus
Twin pairs
chromosome 19
cohort analysis
gene locus
gene mapping
genetic association
genetic linkage
genetic polymorphism
genotype
linkage analysis
lipoprotein blood level
quantitative trait locus
short tandem repeat
twins
Adolescent
Adult
Apolipoprotein E2
Apolipoprotein E3
Apolipoprotein E4
Apolipoproteins E
Chromosomes, Human, Pair 19
Cohort Studies
Female
Genotype
Humans
Linkage (Genetics)
Lod Score
Male
Netherlands
Polymorphism, Genetic
Quantitative Trait, Heritable
Genetta
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DOI
https://doi.org/10.1002/gepi.10318
TNO identifier
237728
ISSN
0741-0395
Source
Genetic Epidemiology, 26 (4), 328-337
Document type
article