Supplement

Gene-Environment interplay in physical, psychological, and cognitive domains in mid to late adulthood: Is APOE a variability gene?

Chandra A. Reynolds1[i], 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 consortium[ii]

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 ofGerontology, 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

Table S1. APOE haplotype frequencies by study among MZ twins.

VETSA / SATSA / OCTO-Twin / MADT / LSADT / TOTAL
APOE haplotype / f / % / f / % / f / % / f / % / f / % / f / %
22 / 0 / 0.00 / 0 / 0.00 / 2 / 1.89 / 1 / 0.26 / 0 / 0.00 / 3 / 0.27
23 / 38 / 11.28 / 20 / 16.00 / 17 / 16.04 / 51 / 13.14 / 21 / 14.19 / 147 / 13.32
24 / 12 / 3.56 / 5 / 4.00 / 3 / 2.83 / 13 / 3.35 / 2 / 1.35 / 35 / 3.17
33 / 192 / 56.97 / 64 / 51.20 / 57 / 53.77 / 208 / 53.61 / 71 / 47.97 / 592 / 53.62
34 / 85 / 25.22 / 32 / 25.60 / 26 / 24.53 / 100 / 25.77 / 50 / 33.78 / 293 / 26.54
44 / 10 / 2.97 / 4 / 3.20 / 1 / 0.94 / 15 / 3.87 / 4 / 2.70 / 34 / 3.08
TOTAL / 337 / 1.00 / 125 / 1.00 / 106 / 1.00 / 388 / 1.00 / 148 / 1.00 / 1104 / 1.00
HWE / χ2 / p / χ2 / p / χ2 / p / χ2 / p / χ2 / p / χ2 / p
3.24 / 0.36 / 1.54 / 0.67 / 1.54 / 0.67 / 1.83 / 0.61 / 5.81 / 0.12 / 3.84 / 0.28

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) / / / delta / se / t / p / p’ / ESr
USA (855) / 0.60 / 0.64 / 0.07 / 0.01 / 6.32 / 2.15E-10 / 1.50E-09 / 0.21
Sweden (581) / 0.54 / 0.53 / 0.07 / 0.01 / 6.38 / 1.85E-10 / 1.48E-09 / 0.26
Denmark (1107) / 0.62 / 0.67 / 0.06 / 0.01 / 5.94 / 1.93E-09 / 1.16E-08 / 0.18
Finland (1007) / 0.63 / 0.70 / 0.07 / 0.01 / 5.89 / 2.67E-09 / 1.33E-08 / 0.18
Men (1734) / 0.55 / 0.54 / 0.06 / 0.01 / 8.36 / 6.21E-17 / 6.84E-16 / 0.20
Women (1816) / 0.66 / 0.76 / 0.08 / 0.01 / 8.04 / 7.76E-16 / 7.76E-15 / 0.19
Depressive Sx (Npair)
USA (754) / 0.73 / 0.95 / 0.11 / 0.02 / 5.87 / 3.17E-09 / 1.90E-08 / 0.21
Sweden (646) / 0.82 / 1.12 / 0.08 / 0.02 / 3.38 / 3.90E-04 / 7.80E-04 / 0.13
Denmark (1099) / 0.90 / 1.54 / 0.25 / 0.02 / 10.20 / 1.04E-23 / 1.14E-22 / 0.29
Finland (1009) / 0.78 / 1.02 / 0.07 / 0.02 / 4.33 / 8.08E-06 / 2.42E-05 / 0.14
Men (1658) / 0.81 / 1.16 / 0.14 / 0.02 / 9.13 / 9.74E-20 / 8.77E-19 / 0.22
Women (1850) / 0.82 / 1.21 / 0.15 / 0.01 / 10.07 / 1.45E-23 / 1.45E-22 / 0.23
Synonyms (Npair)
USA (347) / 0.72 / 0.85 / 0.03 / 0.02 / 1.19 / 1.17E-01 / 3.52E-01 / 0.06
Sweden (565) / 0.59 / 0.58 / 0.04 / 0.01 / 3.07 / 1.11E-03 / 8.86E-03 / 0.13
Denmark (0) / -- / -- / -- / -- / -- / -- / -- / --
Men (547) / 0.69 / 0.76 / 0.03 / 0.02 / 1.54 / 6.26E-02 / 2.50E-01 / 0.07
Women (365) / 0.57 / 0.56 / 0.05 / 0.02 / 3.40 / 3.70E-04 / 3.33E-03 / 0.18
Block Design (Npair)
USA (167) / 0.53 / 0.50 / 0.05 / 0.02 / 2.60 / 5.14E-03 / 3.60E-02 / 0.20
Sweden (226) / 0.59 / 0.62 / 0.08 / 0.02 / 3.68 / 1.47E-04 / 1.17E-03 / 0.24
Denmark (0) / -- / -- / -- / -- / -- / -- / -- / --
Men (151) / 0.57 / 0.62 / 0.11 / 0.03 / 4.02 / 4.58E-05 / 4.12E-04 / 0.31
Women (242) / 0.56 / 0.54 / 0.05 / 0.02 / 2.56 / 5.48E-03 / 3.60E-02 / 0.16
Digits Forward (Npair)
USA (344) / 0.74 / 0.97 / 0.10 / 0.03 / 3.69 / 1.30E-04 / 6.50E-04 / 0.20
Sweden (237) / 0.85 / 1.28 / 0.16 / 0.04 / 3.53 / 2.47E-04 / 9.87E-04 / 0.22
Denmark (970) / 0.86 / 1.28 / 0.11 / 0.02 / 5.03 / 2.96E-07 / 2.37E-06 / 0.16
Men (904) / 0.82 / 1.17 / 0.11 / 0.02 / 5.46 / 3.16E-08 / 3.16E-07 / 0.18
Women (647) / 0.86 / 1.28 / 0.13 / 0.03 / 4.77 / 1.14E-06 / 8.01E-06 / 0.18
Digits Backward (Npair)
USA (518) / 0.88 / 1.32 / 0.10 / 0.03 / 3.20 / 7.41E-04 / 1.48E-03 / 0.14
Sweden (236) / 0.68 / 0.88 / 0.15 / 0.03 / 4.79 / 1.49E-06 / 7.70E-06 / 0.30
Denmark (968) / 0.83 / 1.23 / 0.14 / 0.02 / 6.86 / 6.23E-12 / 6.23E-11 / 0.22
Men (981) / 0.82 / 1.18 / 0.13 / 0.02 / 6.28 / 2.56E-10 / 2.31E-09 / 0.20
Women (741) / 0.83 / 1.25 / 0.15 / 0.02 / 6.17 / 5.50E-10 / 4.40E-09 / 0.22
Symbol Digit (Npair)
USA (213) / 0.58 / 0.54 / 0.01 / 0.02 / 0.53 / 2.97E-01 / 8.92E-01 / 0.04
Sweden (208) / 0.63 / 0.58 / -0.04 / 0.02 / -1.85 / 9.67E-01 / 9.67E-01 / 0.13
Denmark (835) / 0.57 / 0.58 / 0.07 / 0.01 / 6.82 / 8.62E-12 / 9.49E-11 / 0.23
Men (563) / 0.56 / 0.54 / 0.05 / 0.01 / 3.95 / 4.34E-05 / 3.47E-04 / 0.16
Women (693) / 0.60 / 0.60 / 0.04 / 0.01 / 3.35 / 4.26E-04 / 2.99E-03 / 0.13

Note. d = absolute pair difference; delta= ; ; ESr=effect size r = , 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.

[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.