Transcript migration & adhd

Population Migration and the
Variation of Dopamine D4 Receptor
(DRD4) Allele Frequencies Around
the Globe
Moira Maxwell
Dopamine



The neurotransmitter dopamine plays a huge role in the body,
and has been implicated in ADHD
D4 is a dopamine receptor gene that has 2-11 repeat units.
DRD4 in humans is linked to:

Novelty-seeking
 Hyperactivity
 Risk-taking behaviors
•
These are typical ADHD behaviors
Consistent with findings in animal studies:
•
•
•
Increase in exploratory behavior
Increase in speed and locomotion
These behaviors are adaptive for maximizing resources in a
new environment
QuickTime™ and a
decompressor
are needed to see this picture.
Hypotheses

Populations with a history of migration in the
past 1,000 - 30,000 years will show high rates
of DRD4 alleles.
 Macro-migration: Populations that have
migrated many thousands of miles will show
a higher rate of DRD4 alleles than
populations who have not migrated as far.
 Micro-migration: Populations that use
sedentary subsistence strategies will have a
lower percentage of DRD4 alleles than
nomadic populations.
Methods
12 studies with a total sample size of
2,320 individuals with no psychiatric
disorders from 39 countries were
analyzed.
 4,640 alleles looking for the proportion
of 7-repeats the proportion of long
alleles as an index of genotype in a
population

Macro-migration
Estimated in thousands of miles
(kmiles) of population from homeland of
its language family.
 Based on the archeological record and
historical linguistics
 Macro-migrations occured 1,000-30,000
years ago
•
6 Main Migration Routes
American Indians- NE Asia>North
America>Central and South America
 China>Japan/Taiwan/SE Asia/The Pacific
 Jews>Ethiopia/Yemen/Europe
 West Africa>Central/Eastern/Southern Africa
 Black Sea>Europe(Indio Europeans)
 Melanesians>SE Asia

Table 2 (highlight muskoke, guahibo, ticuna, roma
Macro-migration hypothesis

A strong correlation of r =.85 (p<.001)
was found between kmi traveled and
DRD4 long allele frequency distributions
 Supports
hypothesis for macro-migration
 used a solid p-value
Fig 1
C. Chen et al.
of correlations. A more accurate view is that autocorrelation increases the variance
Micro-Migration
Measures survival strategies used by
the 39 societies in this analysis.
 Societies were coded as either
sedentary=0 (28 societies) or as
nomadic=1 (11 societies)
 Nomadic populations had a 10.4%
higher rate of DRD4 long alleles than
sedentary ones.

Micro-migration hypothesis

A correlation of r =.52 (p<.001) was
found between percentage of long
alleles and subsistence type in a
population
 Supports
hypothesis for micro-migration
Macro and micro-migration
Correlation of macro and micromigration was r =.39 (p<.05)
 Regression analysis showed that
macro-migration was a better indicator
of DRD4 allele frequency than micromigration

 For
every kmi away from homeland, the
proportion of DRD4 long alleles increased
by 4.3%
The confound of Auto-correlation

Occurs when sampling units are not independent

Leads to Type I error (rejecting null when it is actually true)
All societies in this study have had contact with other
societies, making it hard to discern if there is an
effect of auto-correlation or not. This is particularly
true of American Indians who are known to share
common ancestry with each other.
• Researchers corrected for this by including all
available data in order to increase sample size
• After correction, hypothesis for macro-migration was
still supported, but not as strongly for micro-migration
as p-value dropped from p<.001 to p<.11
•
Does the bottleneck effect
explain the results?
Populations that are isolated after
migration experience a bottleneck effect
because of a limited gene pool.
 None of the other 128 alleles examined
followed the migratory patterns of the
populations

DRD4 allele frequency and
migration
Correlation found? Yes
 Causation? Three competing
hypotheses

 “Founder’s
effects” or
 “Natural selection/deselection”
 Spontaneous mutation - can rule this out
because r is too high to be by chance
Founder’s effects hypothesis

Populations migrated because of the
genetic makeup of their members
 More
long alleles in population would
increase exploratory behavior which may
increase group migration
 DRD4 allele frequencies seen in early
populations would be the same in modern
populations
Natural selection / deselection

Forced migration due to
 War
 Depletion
of natural resources causing
famine
Natural selection in populations that
adapted to multiple migrations would
cause an increase of DRD4 genes
 In sedentary populations, lack of
migration would cause a deselection of
DRD4 long alleles.

How to test
Ideal solution: Compare genetic data
from populations that is at least 15,000
years old (pre-agriculture) and compare
that with modern genetic data on
frequency of DRD4 alleles.
 This is not possible yet, so the authors
chose the proximate mechanism of
testing DRD4 frequency in modern day
immigrants and in their counterparts
remaining in country of origin.

Table 3
Results
Table 3 shows a lack of support for the
“Founder’s effects” hypothesis as DRD4
frequency rates are the same for
immigrants and non-immigrants
 Founder’s hypothesis and NS/dS
hypothesis are competing, so therefore
the “Natural selection/deselection”
hypothesis is supported.

Natural selection/deselection



Humans began as nomadic foragers who migrated
away from their places of origin repeatedly.
Researchers believe there would have been strong
pressure to select for genes that favored exploratory
behaviors. Repeated migrations would continue to
increase the frequency of these genes.
~15,000 years ago humans began to use agriculture
rather than hunter-gathering. Populations who did not
migrate far after agriculture would have deselected
for migratory genes.
Deselection appears to explain the effects micromigration on DRD4 frequencies.
ADHD
Thought to be a result of selective pressures
on migratory behaviors.
• Very adaptive then, but not in our (almost)
exclusively sedentary modern societies.
• Evolutionary time-lag: If society persists as
sedentary for long enough, a decrease in
ADHD will be seen as it will no longer be
adaptive.
•
Further testing
Testing on non-human primates
 Are there high rates of DRD4 long
alleles in other populations with macromigration?

Global rates of ADHD

Worldwide rate of ADHD is 5.2% (Polanczyk et. al, 2007)

“The North American rate (6.2%) only slightly exceeded the European rate
(4.6%). The highest rates emerged from Africa (8.5%) and South America
(11.8%). Corroboration comes from a dimensional ADHD scale used in 21
countries. Japanese and Finnish children scored lowest, Jamaican and Thai
children scored highest, and American children scored about average.” (Moffitt
and Melchior, 2007)