Effect of APOE ε4 allele on survival and fertility in an adverse environment

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Effect of APOE ε4 allele on survival and fertility in an adverse environment. / van Exel, Eric; Koopman, Jacob J. E.; Bodegom, David van; Meij, Johannes J.; Knijff, Peter de; Ziem, Juventus B.; Finch, Caleb E.; Westendorp, Rudi G J.

In: PLOS ONE, Vol. 12, No. 7, e0179497, 06.07.2017, p. 1-13.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

van Exel, E, Koopman, JJE, Bodegom, DV, Meij, JJ, Knijff, PD, Ziem, JB, Finch, CE & Westendorp, RGJ 2017, 'Effect of APOE ε4 allele on survival and fertility in an adverse environment', PLOS ONE, vol. 12, no. 7, e0179497, pp. 1-13. https://doi.org/10.1371/journal.pone.0179497

APA

van Exel, E., Koopman, J. J. E., Bodegom, D. V., Meij, J. J., Knijff, P. D., Ziem, J. B., ... Westendorp, R. G. J. (2017). Effect of APOE ε4 allele on survival and fertility in an adverse environment. PLOS ONE, 12(7), 1-13. [e0179497]. https://doi.org/10.1371/journal.pone.0179497

Vancouver

van Exel E, Koopman JJE, Bodegom DV, Meij JJ, Knijff PD, Ziem JB et al. Effect of APOE ε4 allele on survival and fertility in an adverse environment. PLOS ONE. 2017 Jul 6;12(7):1-13. e0179497. https://doi.org/10.1371/journal.pone.0179497

Author

van Exel, Eric ; Koopman, Jacob J. E. ; Bodegom, David van ; Meij, Johannes J. ; Knijff, Peter de ; Ziem, Juventus B. ; Finch, Caleb E. ; Westendorp, Rudi G J. / Effect of APOE ε4 allele on survival and fertility in an adverse environment. In: PLOS ONE. 2017 ; Vol. 12, No. 7. pp. 1-13.

Bibtex

@article{f36028e9e34742c6bd54f1a1a776b18e,
title = "Effect of APOE ε4 allele on survival and fertility in an adverse environment",
abstract = "BACKGROUND: The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility.METHODS AND FINDINGS: This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95{\%} confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018).CONCLUSIONS: Contrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.",
keywords = "Adult, Aged, Alleles, Apolipoprotein E4, Communicable Diseases, Drinking Water, Female, Fertility, Gene Expression, Gene Frequency, Ghana, Humans, Male, Middle Aged, Parity, Pregnancy, Prospective Studies, Rural Population, Social Class, Survival Analysis, Journal Article",
author = "{van Exel}, Eric and Koopman, {Jacob J. E.} and Bodegom, {David van} and Meij, {Johannes J.} and Knijff, {Peter de} and Ziem, {Juventus B.} and Finch, {Caleb E.} and Westendorp, {Rudi G J}",
year = "2017",
month = "7",
day = "6",
doi = "10.1371/journal.pone.0179497",
language = "English",
volume = "12",
pages = "1--13",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

RIS

TY - JOUR

T1 - Effect of APOE ε4 allele on survival and fertility in an adverse environment

AU - van Exel, Eric

AU - Koopman, Jacob J. E.

AU - Bodegom, David van

AU - Meij, Johannes J.

AU - Knijff, Peter de

AU - Ziem, Juventus B.

AU - Finch, Caleb E.

AU - Westendorp, Rudi G J

PY - 2017/7/6

Y1 - 2017/7/6

N2 - BACKGROUND: The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility.METHODS AND FINDINGS: This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018).CONCLUSIONS: Contrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.

AB - BACKGROUND: The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility.METHODS AND FINDINGS: This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018).CONCLUSIONS: Contrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.

KW - Adult

KW - Aged

KW - Alleles

KW - Apolipoprotein E4

KW - Communicable Diseases

KW - Drinking Water

KW - Female

KW - Fertility

KW - Gene Expression

KW - Gene Frequency

KW - Ghana

KW - Humans

KW - Male

KW - Middle Aged

KW - Parity

KW - Pregnancy

KW - Prospective Studies

KW - Rural Population

KW - Social Class

KW - Survival Analysis

KW - Journal Article

U2 - 10.1371/journal.pone.0179497

DO - 10.1371/journal.pone.0179497

M3 - Journal article

VL - 12

SP - 1

EP - 13

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 7

M1 - e0179497

ER -

ID: 185192675