The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease

Chang En Yu, Haydeh Payami, Jane M. Olson, Michael Boehnke, Ellen M. Wijsman, Harry T. Orr, Walter A. Kukull, Katrina A B Goddard, Ellen Nemens, June A. White, M. Elisa Alonso, Todd D. Taylor, Melvyn J. Ball, Jeffrey Kaye, John Morris, Helena Chui, Adele D. Sadovnick, George M. Martin, Eric B. Larson, Leonard L. HestonThomas D. Bird, Gerard D. Schellenberg

Research output: Contribution to journalArticle

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Abstract

The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset -9; and Z(SND) = 4.07, P <.00005, respectively). No association between the ε4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between ε4 and AD was also observed in a group of unrelated subjects; the ε4 frequency was .26 in affected subjects, versus .19 in controls (Z(SND) = 2.20, P <.03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained (model 1, maximum Z [Z(max)] = 0.61, recombination fraction [θ] = .30; model 2, Z(max) = 0.47, θ = .20). For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls (model 1, Z(max) = 2.02, θ = .15; model 2, Z(max) = 3.42, θ = .05) or allele frequencies from the families (model 1, Z(max) = 1.43, θ = .15; model 2, Z(max) = 1.70, θ = .05) were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased (model 1, Z(max) = 3.17, θ = .23; model 3, Z(max) = 1.85, θ = .20). For the ENVG group, results for ApoE and ApoCII were uniformly negative. Affected-pedigree- member analysis gave significant results for the late-onset kindreds, for ApoE (Z(SND) = 3.003, P = .003) and ApoCII (Z(SND) = 2.319, P = .016), when control allele frequencies were used but not when allele frequencies were derived from the families.

Original languageEnglish (US)
Pages (from-to)631-642
Number of pages12
JournalAmerican Journal of Human Genetics
Volume54
Issue number4
StatePublished - 1994

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Phentolamine
Apolipoproteins E
Multigene Family
Alzheimer Disease
Gene Frequency
Penetrance
Lod Score
Chromosomes, Human, Pair 19
Linkage Disequilibrium
Pedigree
Age of Onset
Genetic Recombination
Alleles

ASJC Scopus subject areas

  • Genetics

Cite this

Yu, C. E., Payami, H., Olson, J. M., Boehnke, M., Wijsman, E. M., Orr, H. T., ... Schellenberg, G. D. (1994). The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease. American Journal of Human Genetics, 54(4), 631-642.

The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease. / Yu, Chang En; Payami, Haydeh; Olson, Jane M.; Boehnke, Michael; Wijsman, Ellen M.; Orr, Harry T.; Kukull, Walter A.; Goddard, Katrina A B; Nemens, Ellen; White, June A.; Alonso, M. Elisa; Taylor, Todd D.; Ball, Melvyn J.; Kaye, Jeffrey; Morris, John; Chui, Helena; Sadovnick, Adele D.; Martin, George M.; Larson, Eric B.; Heston, Leonard L.; Bird, Thomas D.; Schellenberg, Gerard D.

In: American Journal of Human Genetics, Vol. 54, No. 4, 1994, p. 631-642.

Research output: Contribution to journalArticle

Yu, CE, Payami, H, Olson, JM, Boehnke, M, Wijsman, EM, Orr, HT, Kukull, WA, Goddard, KAB, Nemens, E, White, JA, Alonso, ME, Taylor, TD, Ball, MJ, Kaye, J, Morris, J, Chui, H, Sadovnick, AD, Martin, GM, Larson, EB, Heston, LL, Bird, TD & Schellenberg, GD 1994, 'The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease', American Journal of Human Genetics, vol. 54, no. 4, pp. 631-642.
Yu CE, Payami H, Olson JM, Boehnke M, Wijsman EM, Orr HT et al. The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease. American Journal of Human Genetics. 1994;54(4):631-642.
Yu, Chang En ; Payami, Haydeh ; Olson, Jane M. ; Boehnke, Michael ; Wijsman, Ellen M. ; Orr, Harry T. ; Kukull, Walter A. ; Goddard, Katrina A B ; Nemens, Ellen ; White, June A. ; Alonso, M. Elisa ; Taylor, Todd D. ; Ball, Melvyn J. ; Kaye, Jeffrey ; Morris, John ; Chui, Helena ; Sadovnick, Adele D. ; Martin, George M. ; Larson, Eric B. ; Heston, Leonard L. ; Bird, Thomas D. ; Schellenberg, Gerard D. / The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease. In: American Journal of Human Genetics. 1994 ; Vol. 54, No. 4. pp. 631-642.
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title = "The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease",
abstract = "The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset -9; and Z(SND) = 4.07, P <.00005, respectively). No association between the ε4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between ε4 and AD was also observed in a group of unrelated subjects; the ε4 frequency was .26 in affected subjects, versus .19 in controls (Z(SND) = 2.20, P <.03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1{\%}) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained (model 1, maximum Z [Z(max)] = 0.61, recombination fraction [θ] = .30; model 2, Z(max) = 0.47, θ = .20). For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls (model 1, Z(max) = 2.02, θ = .15; model 2, Z(max) = 3.42, θ = .05) or allele frequencies from the families (model 1, Z(max) = 1.43, θ = .15; model 2, Z(max) = 1.70, θ = .05) were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased (model 1, Z(max) = 3.17, θ = .23; model 3, Z(max) = 1.85, θ = .20). For the ENVG group, results for ApoE and ApoCII were uniformly negative. Affected-pedigree- member analysis gave significant results for the late-onset kindreds, for ApoE (Z(SND) = 3.003, P = .003) and ApoCII (Z(SND) = 2.319, P = .016), when control allele frequencies were used but not when allele frequencies were derived from the families.",
author = "Yu, {Chang En} and Haydeh Payami and Olson, {Jane M.} and Michael Boehnke and Wijsman, {Ellen M.} and Orr, {Harry T.} and Kukull, {Walter A.} and Goddard, {Katrina A B} and Ellen Nemens and White, {June A.} and Alonso, {M. Elisa} and Taylor, {Todd D.} and Ball, {Melvyn J.} and Jeffrey Kaye and John Morris and Helena Chui and Sadovnick, {Adele D.} and Martin, {George M.} and Larson, {Eric B.} and Heston, {Leonard L.} and Bird, {Thomas D.} and Schellenberg, {Gerard D.}",
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T1 - The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease

AU - Yu, Chang En

AU - Payami, Haydeh

AU - Olson, Jane M.

AU - Boehnke, Michael

AU - Wijsman, Ellen M.

AU - Orr, Harry T.

AU - Kukull, Walter A.

AU - Goddard, Katrina A B

AU - Nemens, Ellen

AU - White, June A.

AU - Alonso, M. Elisa

AU - Taylor, Todd D.

AU - Ball, Melvyn J.

AU - Kaye, Jeffrey

AU - Morris, John

AU - Chui, Helena

AU - Sadovnick, Adele D.

AU - Martin, George M.

AU - Larson, Eric B.

AU - Heston, Leonard L.

AU - Bird, Thomas D.

AU - Schellenberg, Gerard D.

PY - 1994

Y1 - 1994

N2 - The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset -9; and Z(SND) = 4.07, P <.00005, respectively). No association between the ε4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between ε4 and AD was also observed in a group of unrelated subjects; the ε4 frequency was .26 in affected subjects, versus .19 in controls (Z(SND) = 2.20, P <.03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained (model 1, maximum Z [Z(max)] = 0.61, recombination fraction [θ] = .30; model 2, Z(max) = 0.47, θ = .20). For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls (model 1, Z(max) = 2.02, θ = .15; model 2, Z(max) = 3.42, θ = .05) or allele frequencies from the families (model 1, Z(max) = 1.43, θ = .15; model 2, Z(max) = 1.70, θ = .05) were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased (model 1, Z(max) = 3.17, θ = .23; model 3, Z(max) = 1.85, θ = .20). For the ENVG group, results for ApoE and ApoCII were uniformly negative. Affected-pedigree- member analysis gave significant results for the late-onset kindreds, for ApoE (Z(SND) = 3.003, P = .003) and ApoCII (Z(SND) = 2.319, P = .016), when control allele frequencies were used but not when allele frequencies were derived from the families.

AB - The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset -9; and Z(SND) = 4.07, P <.00005, respectively). No association between the ε4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between ε4 and AD was also observed in a group of unrelated subjects; the ε4 frequency was .26 in affected subjects, versus .19 in controls (Z(SND) = 2.20, P <.03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained (model 1, maximum Z [Z(max)] = 0.61, recombination fraction [θ] = .30; model 2, Z(max) = 0.47, θ = .20). For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls (model 1, Z(max) = 2.02, θ = .15; model 2, Z(max) = 3.42, θ = .05) or allele frequencies from the families (model 1, Z(max) = 1.43, θ = .15; model 2, Z(max) = 1.70, θ = .05) were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased (model 1, Z(max) = 3.17, θ = .23; model 3, Z(max) = 1.85, θ = .20). For the ENVG group, results for ApoE and ApoCII were uniformly negative. Affected-pedigree- member analysis gave significant results for the late-onset kindreds, for ApoE (Z(SND) = 3.003, P = .003) and ApoCII (Z(SND) = 2.319, P = .016), when control allele frequencies were used but not when allele frequencies were derived from the families.

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