Genetic Contribution to Rate of Change in Functional Abilities among Danish Twins Aged 75 Years or More
Kaare Christensen
)
1
2
3
David Gaist
1
2
3
James W. Vaupel
2
3
Matt McGue
3
4
0
Max Planck Institute for Demographic Research
,
Rostock D- 18057
,
Germany
1
Danish Center for Demographic Research, Odense University
,
DK-5000 Odense
,
Denmark
2
Danish Twin Registry, Institute of Public Health, University of Southern Denmark
,
DK-5000 Odense
,
Denmark
3
Received for publication March 7
,
2001, and accepted for publi- cation July 19, 2001. Abbreviation: LSADT
,
Longitudinal Study of Aging Danish Twins
4
Department of Psychology, University of Minnesota
,
Minneapolis
,
MN. Reprint requests to Dr. Kaare Christensen, Institute of Public Health, University of Southern Denmark
,
Sndre Boulevard 23A, DK- 5000 Odense C
,
Denmark (
In a previous cross-sectional study of twins, the authors found evidence of a substantial genetic influence on functional abilities among elderly women. It has been suggested that rate of change in functional abilities over time could underlie such findings and that rate-of-change phenotypes may have an even larger genetic component than level phenotypes (e.g., functional abilities per se). If so, rate-of-change phenotypes could be more powerful than level phenotypes in studies aimed at identifying specific polymorphisms of importance for aging. In 1995, the authors assessed a population-based sample of 2,401 Danish twins aged 75 years or more. The survivors were recontacted after 2 years and again after 4 years. Consistent mean-level declines, high within-person correlations over time, and substantial heritability in the female sample were observed for functional abilities. Nonetheless, structural-equation analyses revealed only a very modest and nonsignificant heritability for rate of change in functional abilities: 16% (95% confidence interval: 0, 35) for women and 9% (95% confidence interval: 0, 44) for men. This study had a large initial sample size, high participation rates, and a valid and reliable measure of rate of change in a phenotype that had previously shown substantial heritability in crosssectional analyses in the same twin population. Still, the present study revealed only a modest and nonsignificant genetic influence on rate of change, which suggests that detection of polymorphisms influencing rate of change in functional abilities among the elderly may prove to be difficult. Am J Epidemiol 2002;155: 132-9. activities of daily living; aging; genetics; twin studies; twins; variation (genetics)
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Animal models using nematodes, Drosophila flies, and
mice have clearly demonstrated that single genes can have a
substantial influence on aging and life-span (13). In
humans, premature aging syndromes such as Werners
syndrome also show how mutations in single genes can affect
aging and survival (4). Such mutations are rare, but the
apolipoprotein E polymorphism provides evidence for more
common genetic variants which influence cognitive
abilities, disease occurrence, and survival at older ages (5).
The apolipoprotein E polymorphism is the only common
polymorphism known to influence the aging process in
humans. However, previous studies (including studies of
twins) have suggested that in contemporary populations in
the industrial world, approximately one quarter of the
variation in life-span can be attributed to genetic factors (68).
There is evidence that cognitive and functional abilities
have an even larger genetic component: A Swedish twin
study showed that approximately half of the variation in
cognitive abilities among persons aged 80 years was due to
genetic factors (9), and a recent Danish twin study showed
that one third to one half of the variation in functional
abilities among women aged 80 years could be attributed to
genetic variation (10).
Both of these studies were cross-sectional, and it has been
suggested that rate-of-change patterns underlie such
observationsi.e., that genetic factors influence capabilities
more through the rate of decline than through the starting
value or level value (11). If this is the case, rate of change
may be a more heritable and therefore more powerful
phenotype than level phenotypes for research aimed at
identifying genes that influence aging processes. However, at
present, few data on the genetic contribution to
rate-ofchange phenotypes are available, and the data have
generally shown lower heritability of rate of change than of the
phenotypes in cross-sectional analyses (1215).
In the present study, we sought to estimate the genetic
contribution to rate of change in functional abilities among
the elderly by using data from the Longitudinal Study of
Aging Danish Twins (LSADT). The LSADT started out
with assessment of 2,401 Danish twins aged 75 years in
1995. The survivors were revisited after 2 years and again
after 4 years. A total of 984 individuals, including 127 twin
pairs, participated in all three ability assessments.
MATERIALS AND METHODS
Study population
The LSADT has previously been described in detail (10,
1621). In brie (...truncated)