SUPPLEMENT
Gene-Environment interplay in physical, psychological, and cognitive domains in mid to
late adulthood: Is APOE a variability gene?
Chandra A. Reynolds1i, Margaret Gatz2,3, Kaare Christensen4,5, Lene Christiansen4, Anna K.
Dahl Aslan6,3, Jaakko Kaprio7, Tellervo Korhonen8, William S. Kremen9, Robert Krueger10, Matt
McGue10,4, Jenae M. Neiderhiser11, and Nancy L. Pedersen3,2 for the iGEMS consortiumii
1. Department of Psychology, University of California Riverside, Riverside, CA 92521 USA
2. Department of Psychology, University of Southern California, Los Angeles, CA 90089 USA
3. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-17177
Stockholm, Sweden
4. Epidemiology, Biostatistics and Bio-demography, Institute of Public Health, University of
Southern Denmark, DK-5000, Odense C, Denmark
5. Department of Clinical Genetics and Department of Clinical Biochemistry and Pharmacology,
Odense University Hospital, Odense, Denmark
6. Institute of Gerontology, School of Health and Welfare, Jönköping University, Jönköping,
Sweden
7. Department of Public Health & Institute for Molecular Medicine FIMM, University of
Helsinki, FI-00014, Finland
8. Department of Public Health, University of Helsinki & Institute of Public Health and Clinical
Nutrition, University of Eastern Finland, FI- 00014, Finland
9. Department of Psychiatry, University of California San Diego, La Jolla, CA 92093 USA
10. Department of Psychology, University of Minnesota, Minneapolis, MN, 55455 USA
11. Department of Psychology, The Pennsylvania State University, University Park, PA, USA
i
To whom correspondence should be addressed: Chandra A. Reynolds, Professor, Department of
Psychology, University of California Riverside, 900 University Ave., Riverside, CA 92521 USA.
TEL:+1-951-827-2430; FAX: +1-951-827-3985.
ii
Members of the consortium on Interplay of Genes and Environment across Multiple Studies
(IGEMS) are listed in the manuscript appendix.
Table S1. APOE haplotype frequencies by study among MZ twins.
VETSA
SATSA
OCTO-Twin
MADT
LSADT
TOTAL
APOE
haplotype
22
23
24
33
34
44
TOTAL
f
%
f
%
f
%
f
%
f
%
f
%
0
38
12
192
85
10
337
0.00
11.28
3.56
56.97
25.22
2.97
1.00
0
20
5
64
32
4
125
0.00
16.00
4.00
51.20
25.60
3.20
1.00
2
17
3
57
26
1
106
1.89
16.04
2.83
53.77
24.53
0.94
1.00
1
51
13
208
100
15
388
0.26
13.14
3.35
53.61
25.77
3.87
1.00
0
21
2
71
50
4
148
0.00
14.19
1.35
47.97
33.78
2.70
1.00
3
147
35
592
293
34
1104
0.27
13.32
3.17
53.62
26.54
3.08
1.00
HWE
χ2
p
0.36
χ2
p
0.67
χ2
p
0.67
χ2
p
0.61
p
0.12
χ2
p
0.28
3.24
1.54
1.54
1.83
χ2
5.81
3.84
Note. HWE = Hardy-Weinberg Equilibrium test. Only one member of each MZ pair was tallied
in the above frequencies.
Table S2. Test of mixture distributions of MZ within pair differences by Country and Sex.
BMI (Npair)
USA (855)
Sweden (581)
Denmark (1107)
Finland (1007)
Men (1734)
Women (1816)
Depressive Sx (Npair)
USA (754)
Sweden (646)
Denmark (1099)
Finland (1009)
Men (1658)
Women (1850)
Synonyms (Npair)
USA (347)
Sweden (565)
Denmark (0)
Men (547)
Women (365)
Block Design (Npair)
USA (167)
Sweden (226)
Denmark (0)
Men (151)
Women (242)
Digits Forward (Npair)
USA (344)
Sweden (237)
Denmark (970)
Men (904)
Women (647)
Digits Backward
(Npair)
USA (518)
Sweden (236)
Denmark (968)
Men (981)
Women (741)
Symbol Digit (Npair)
USA (213)
Sweden (208)
Denmark (835)
Men (563)
Women (693)
0.64
0.53
0.67
0.70
0.54
0.76
delta
0.07
0.07
0.06
0.07
0.06
0.08
se
0.01
0.01
0.01
0.01
0.01
0.01
t
6.32
6.38
5.94
5.89
8.36
8.04
p
2.15E-10
1.85E-10
1.93E-09
2.67E-09
6.21E-17
7.76E-16
p’
ESr
1.50E-09 0.21
1.48E-09 0.26
1.16E-08 0.18
1.33E-08 0.18
6.84E-16 0.20
7.76E-15 0.19
0.73
0.82
0.90
0.78
0.81
0.82
0.95
1.12
1.54
1.02
1.16
1.21
0.11
0.08
0.25
0.07
0.14
0.15
0.02
0.02
0.02
0.02
0.02
0.01
5.87
3.38
10.20
4.33
9.13
10.07
3.17E-09
3.90E-04
1.04E-23
8.08E-06
9.74E-20
1.45E-23
1.90E-08
7.80E-04
1.14E-22
2.42E-05
8.77E-19
1.45E-22
0.21
0.13
0.29
0.14
0.22
0.23
0.72
0.59
-0.69
0.57
0.85
0.58
-0.76
0.56
0.03
0.04
-0.03
0.05
0.02
0.01
-0.02
0.02
1.19
3.07
-1.54
3.40
1.17E-01 3.52E-01
1.11E-03 8.86E-03
--6.26E-02 2.50E-01
3.70E-04 3.33E-03
0.06
0.13
-0.07
0.18
0.53
0.59
-0.57
0.56
0.50
0.62
-0.62
0.54
0.05
0.08
-0.11
0.05
0.02
0.02
-0.03
0.02
2.60
3.68
-4.02
2.56
5.14E-03
1.47E-04
-4.58E-05
5.48E-03
3.60E-02
1.17E-03
-4.12E-04
3.60E-02
0.20
0.24
-0.31
0.16
0.74
0.85
0.86
0.82
0.86
0.97
1.28
1.28
1.17
1.28
0.10
0.16
0.11
0.11
0.13
0.03
0.04
0.02
0.02
0.03
3.69
3.53
5.03
5.46
4.77
1.30E-04
2.47E-04
2.96E-07
3.16E-08
1.14E-06
6.50E-04
9.87E-04
2.37E-06
3.16E-07
8.01E-06
0.20
0.22
0.16
0.18
0.18
0.88
0.68
0.83
0.82
0.83
1.32
0.88
1.23
1.18
1.25
0.10
0.15
0.14
0.13
0.15
0.03
0.03
0.02
0.02
0.02
3.20
4.79
6.86
6.28
6.17
7.41E-04
1.49E-06
6.23E-12
2.56E-10
5.50E-10
1.48E-03
7.70E-06
6.23E-11
2.31E-09
4.40E-09
0.14
0.30
0.22
0.20
0.22
0.58
0.63
0.57
0.56
0.60
0.54
0.58
0.58
0.54
0.60
0.01
-0.04
0.07
0.05
0.04
0.02
0.02
0.01
0.01
0.01
0.53
-1.85
6.82
3.95
3.35
2.97E-01 8.92E-01
9.67E-01 9.67E-01
8.62E-12 9.49E-11
4.34E-05 3.47E-04
4.26E-04 2.99E-03
0.04
0.13
0.23
0.16
0.13
d
d2
0.60
0.54
0.62
0.63
0.55
0.66
𝜋
Note. d = absolute pair difference; delta= ̅̅̅
𝑑 2 − 2 𝑑̅ 2 ; 𝑠𝑒 =
̅̅̅̅
𝑑2
√𝑛
(.5321); ESr=effect size r =
𝑡2
√(𝑡 2 +𝑑𝑓) , where df=Npair-1. p-values are based on one-tailed t-tests; bolded p-values are
signficant according to FDR tests. p' = Holm-Bonferroni sequentially adjusted p-values, where
bolded are signficant.