Introduction 2000 2007 2005 1995 2001 1983 1993 2000 2001 2003 1992 2001 1994a 1998 2000 1994a 1983 1999 1998 1992 2001 1996 2002 1996 1998 2002 2005 . 2002 1992 1999 2005 2006 2002 2005 . 2005 1982 1968 2001 . 1998 1998 1897 1983 1994 1998 1983 1959 1983 2004 2006 1999 2000 To summarize, in this report, we address the following questions. First, is there spousal similarity for blood-injury, social and agoraphobic fear? Second, what are the heritability estimates for these three subtypes of fear? Third, are there sex and age differences in the heritability estimates of these subtypes? Methods Participants 2006 2002 2004 2006 1 n n Table 1 Family configuration in the sample according to zygosity, cohort and number of additional non-twin siblings of the two time points (separated by the slash; 1997/2000)   Zero siblings Brother Sister Brother and Sister Total Age 14–25 MZM Twin pair 70/104 41/29 35/27 9/4 155/164 Single twin 21/57 4/6 10/11 1/3 36/77 DZM Twin pair 44/45 33/15 26/14 3/7 106/81 Single twin 18/44 4/9 10/10 1/2 33/65 MZF Twin pair 145/230 49/35 62/56 12/9 268/330 Single twin 49/106 10/12 11/17 3/2 73/137 DZF Twin pair 84/108 34/19 37/27 7/7 162/161 Single twin 33/87 10/9 12/23 2/2 57/121 DOS Twin pair 101/105 64/37 68/41 10/3 243/186 Single twin 69/183 11/26 25/32 6/2 111/243 No twins   23/43 38/72 2/4 63/119 Total age 14–25  634/1069 283/240 334/330 56/45 1307/1684 Age 26–65 MZM Twin pair 16/60 8/6 7/11 5/8 36/85 Single twin 20/68 6/3 4/7 6/1 36/79 DZM Twin pair 11/31 3/6 3/7 7/3 24/47 Single twin 20/54 4/2 7/5 5/5 36/66 MZF Twin pair 64/223 14/22 23/53 9/12 110/310 Single twin 30/122 6/10 10/16 2/4 48/152 DZF Twin pair 29/95 8/14 11/15 3/6 51/130 Single twin 39/99 4/9 14/7 3/0 60/115 DOS Twin pair 27/86 9/7 10/15 4/7 50/115 Single twin 36/120 6/8 10/22 6/5 58/155 No twins   21/44 46/25 12/8 79/77 Total age 26–65  292/958 89/131 145/183 62/59 588/1331 Total number of families  926/2027 372/371 479/513 118/104 1895/3015 MZM = monozygotic males; DZM = dizygotic males; MZF = monozygotic females; DZF = dizygotic females; DOS = dizygotic opposite sex twins Zygosity n n 2005 Measures 1979 1988 Twin-family Studies Twin studies make use of the genetic relatedness of twins and their family members to address questions about the etiology of population variation. Monozygotic (MZ) twins are genetically (nearly) identical. Dizygotic (DZ) twins and siblings share on average 50% of their segregating genes. Additive genetic effects (A) are suggested if the correlation for a phenotype in MZ twins is larger than the correlation in DZ twins and siblings. When the DZ correlation is more than half the MZ correlation, this indicates environmental effects shared by members from the same family (C). When the DZ correlation is less than half the MZ correlation, this can be taken as evidence for non-additive genetic effects (D). Non-additive genetic effects can consist of interactions between alleles within a locus (dominance) or across different loci (epistasis). Differences in fear scores within MZ twin pairs are due to unique environmental influences (E), which also include measurement error. The observed variance in phobic fear can thus be decomposed in four possible sources of variance; A, C, D, and E. However, the observed variances and covariances only provide enough information to test either an ACE model or an ADE model. Based on the pattern of twin correlations (see results section), A, D, and E were modelled in this study. Statistical Analysis 1 2004 2 1996 P Fig. 1 Threshold model of the liability for phobic fear. Latent factors are symbolized in circles, observed phenotype as squares. E, unique environmental factor; D, non-additive genetic factor; A, additive genetic factor; L, liability for phobic fear. Latent factors can be correlated within families and influence the liability to phobic fear  Fig. 2 Y  2003 2 2 P- , 2006 First, we tested whether the resemblance in sibling pairs was the same as in dizygotic twin pairs. Next, quantitative sex differences were investigated by constraining the correlations for same-sex male twin pairs and same-sex female twin pairs to be equal. Qualitative sex differences were investigated by constraining the correlations for DZ same-sex twin pairs and DZ opposite-sex twin pairs to be equal. In a genetic model, the influence of latent factors A, D and E on the phobic fear score in 1997 and 2000 was estimated by the parameters (factor loadings) a, d, and e. The estimates for a, d and e were constrained to be equal in 1997 and 2000 for all three fear subtypes because we assume that the same etiological mechanism influences phobic fear at both time points. Correlations between the latent A and D factors were fixed at 1 for MZ twins. For DZ twins and siblings, the correlations between the latent A factors were fixed at 0.5, because they share on average half of their segregating genes. Dominant genetic effects result from the interaction or combination of alleles at a particular locus. Offspring receive only one allele from each parent and not a combination of two alleles. Parents and offspring share on average half of their genes so the chance that two siblings receive the same allele is 0.5 × 0.5 resulting in a correlation of 0.25 between the latent D factor for DZ twins and sibling pairs. We first tested whether a, d and e in the two age groups could be constrained to be equal. Next, different models (ADE, AE and E) were fitted to the data to test which sources of variance contribute to individual differences in phobic fear. Results 2 r s P r s P r s P 2 Table 2 Twin and sibling correlations for blood-injury, social and agoraphobic fear for age group 14–25 years and age group 26–65 years (95% confidence intervals added in parentheses)  Blood-injury fear  Social fear Agoraphobic fear Age 14–25 Age 26–65 Age 14–25 Age 26–65 Age 14–25 Age 26–65 MZ males 0.30 (0.17–0.42) 0.36 (0.14–0.54) 0.53 (0.41–0.63) 0.29 (0.03–0.50) 0.47 (0.34–0.56) 0.49 (0.27–0.65) DZ males 0.04 (−0.16–0.22) −0.04 (−0.32–0.25) 0.15 (−0.05–0.34) 0.49 (0.20–0.68) 0.27 (0.09–0.43) 0.22 (−0.10–0.48) MZ females 0.34 (0.25–0.43) 0.41 (0.32–0.50) 0.48 (0.39–0.56) 0.42 (0.31–0.52) 0.40 (0.30–0.48) 0.37 (0.26–0.47) DZ females 0.18 (0.05–0.30) 0.11 (−0.06–0.28) 0.20 (0.06–0.33) 0.37 (0.20–0.53) 0.13 (−0.00–0.26) 0.27 (0.08–0.44) DZ opposite sex 0.23 (0.10–0.34) 0.16 (−0.04–0.34) 0.22 (0.10–0.34) 0.25 (0.03–0.44) 0.17 (0.04–0.29) 0.22 (0.01–0.41) Brother–brother 0.16 (0.03–0.28) 0.28 (0.10–0.44) 0.12 (−0.02–0.25) 0.19 (−0.03–0.38) 0.09 (−0.04–0.22) −0.01 (−0.24–0.22) Sister–sister 0.10 (−0.01–0.20) −0.02 (−0.16–0.13) 0.09 (−0.03–0.20) 0.14 (−0.01–0.28) 0.10 (−0.01–0.19) 0.12 (−0.03–0.26) Brother–sister 0.10 (0.02–0.18) 0.06 (−0.05–0.17) 0.15 (0.06–0.23) 0.11 (−0.02–0.23) 0.08 (−0.00–0.02) 0.07 (−0.05–0.18) a 0.33 (0.26–0.40) 0.39 (0.30–0.48) 0.50 (0.43–0.56) 0.40 (0.30–0.49) 0.42 (0.35–0.49) 0.39 (0.30–0.48) a 0.13 (0.08–0.18) 0.09 (0.02–0.16) 0.15 (0.10–0.20) 0.20 (0.13–0.27) 0.11 (0.07–0.16) 0.12 (0.05–0.19) MZ = monozygotic; DZ = dizygotic a 3 4 Table 3 Model fitting results for blood-injury, social, and agoraphobic fear; comparisons of models are shown Models vs −2LL df Δdf 2 P Blood-injury fear 1. ADE  20254.58 9608    2. ADE no age diff. 1 20257.23 9617 9 2.65 0.98 3. AE no age diff. 2 20415.27 9620 3 158.03 0.00 Social fear 1. ADE  19439.72 9608    2. ADE no age diff. 1 19468.90 9617 9 29.18 0.00 3. AE young  ADE old 1 19454.05 9611 3 14.33 0.00 4. ADE young  AE old 1 19439.72 9611 3 0.00 1.00 5. ADE young  E old 4 19521.58 9614 3 81.87 0.00 Agoraphobic fear 1. ADE   19967.61 9614    2. ADE no age diff. 1 19973.66 9623 9 6.05 0.74 3. AE no age diff. 2 19984.90 9626 3 11.24 0.01 vs = versus and indicates which model the sub model is compared to; −2LL = −2 log likelihood; df = degrees of freedom Most parsimonious solution per fear subtype is shown in bold Table 4 Parameter estimates of the best-fitting models in age group 14–25 and age group 26–65 for blood-injury fear, social fear and agoraphobic fear   2 2 2 Blood-injury fear Age 14–65 9.9 25.6 64.5 Social fear Age 14–25 7.8 42.9 49.3 Age 26–65 40.3 – 59.7 Agoraphobic fear Age 14–65 10.7 29.9 59.5 2 2 2 Comments This is the first study that explored the genetic and environmental contributions to individual differences in blood-injury, social, and agoraphobic fear using an extended twin design. We tested whether there was evidence for assortative mating, for a specific twin environment, and if the impact of the genetic and environmental factors differed between men and women and between two age cohorts. 1998 1994 2005 2002 1994 1987 1998 2007 1992 2001 2005 2005 2006 1992 2005 2005 2002 2002 2005 2000 1994b 1983 1999 1998 2002 2004 2001 1992 In summary, we found random mating for blood-injury, social and agoraphobic fear. Individual differences in blood-injury fear and agoraphobic fear in both age groups and social fear in the youngest age group (14–25 years) could be explained by additive and non-additive genetic factors and unique environmental factors, while individual differences in social fear in the oldest age group (26–65 years) could be explained by additive genetic and unique environmental factors. The heritability of the three fear subtypes was similar for men and women and no effects of sex-specific genes were detected.