Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype
Abstract
:1. Introduction
2. Results
2.1. Hypothesis 1: Multiple Individuals in Large Families Demonstrate the BAP
2.2. Hypothesis 2: Specific BAP Endophenotypes Exist Across BAP Domains
2.3. Hypothesis 3: BAP Endophenotypes Vary in Large Multiplex Families
2.4. Correlates of the BAP Endophenotypes
3. Discussion
4. Materials and Methods
4.1. Large Multiplex Families
4.2. Protocol for Diagnosing ASD in Large Multiplex Families
4.3. Protocol for Phenotyping the BAP in Large Multiplex Families
4.4. Small Families
4.5. Endophenotyping Procedure
4.5.1. Step 1: Identification of Potential BAP Endophenotypes in Large Multiplex Families
4.5.2. Step 2: Validation of BAP Endophenotypes in Small Families
4.5.3. Step 3: Assessment of BAP Endophenotypes in Family A and B
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Data Availability
References
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Participants (n) (Female) | Mean Age (Range) | Cognitive Data (n) | FSIQ Mean (SD) | VIQ Mean (SD) | PIQ Mean (SD) | |
---|---|---|---|---|---|---|
Family A | ||||||
ASD | 7 (1) | 11.43 (4–34) | 5 | 107 (16) | 97 (15) | 101 (30) |
Unaffected | 6 (5) | 25.83 (2–50) | 5 | 127 (17) | 130 (17) | 117 (15) |
BAP | 17 (8) | 49.18 (13–79) | 16 a | 119 (13) | 117 (13) | 115 (12) |
Total | 30 (14) | 35.7 (2–79) | 26 | 118 (15) | 116 (17) | 113 (18) |
Family B | ||||||
ASD | 9 (3) | 15.00 (8–20) | 5 | 95 (20) | 89 (28) | 105 (16) |
Unaffected | 9 (7) | 37.33 (10–73) | 9 | 110 (14) | 111 (14) | 108 (11) |
BAP | 15 (10) | 47.40 (15–73) | 15 | 102 (17) | 105 (18) | 99 (17) |
Total | 33 (20) | 35.06 (6–73) | 29 | 103 (17) | 104 (19) | 102 (15) |
Total | 63 (34) | 35.37 (2–79) | 55 a | 110 (18) | 110 (19) | 107 (17) |
Mean Proportional Score (SD) | Cut-off Score | BAP Traits | |
---|---|---|---|
Unaffected (n = 11) | BAP (n = 30) | ||
‘Socially unaware’: Poor self-regulation and reciprocity in conversation | |||
0.20 (0.18) | 0.69 (0.06) ** | >0.17 |
|
‘Pedantic’: Self-focused and technical in interactions | |||
0.04 (0.05) | 0.11 (0.12) * | >0.14 |
|
‘Aloof’: Difficulties relating to other’s emotions and expressing own emotions | |||
0.12 (0.07) | 0.31 (0.16) *** | >0.20 |
|
‘Obsessive’: Regimented approach to life and tendency to ruminate | |||
0.13 (0.10) | 0.27 (0.18) *** | >0.25 |
|
Endophenotypes | ||||||
---|---|---|---|---|---|---|
Domain | Task | Socially Unaware | Pedantic | Aloof | Obsessive | Total Number |
Social communication | PRS | 0.83 ** | 0.73 ** | 0.76 ** | 0.45 ** | 0.86 ** |
FPT | −0.43 ** | −0.28 | −0.24 | −0.18 | −0.40 ** | |
Intellect | FSIQ | −0.36 * | −0.10 | −0.31 * | −0.02 | −0.28 |
VIQ | −0.29 | −0.05 | −0.31 * | −0.03 | −0.28 | |
PIQ | −0.36 * | −0.13 | −0.19 | −0.02 | −0.26 | |
Executive functions | Trails (numbers) a | −0.32 * | −0.20 | −0.29 | 0.17 | −0.19 |
Trails (switch) a | −0.24 | −0.23 | −0.27 | −0.22 | −0.34 * | |
Design fluency (switch) a | −0.27 | −0.25 | −0.15 | −0.09 | −0.34 * | |
Design fluency (composite) a | −0.27 | −0.25 | −0.25 | −0.03 | −0.32 * | |
Tower task (achievement) a | −0.40 ** | −0.19 | −0.27 | −0.22 | −0.26 | |
Sorting (confirmed) | −0.33 * | −0.23 | −0.32 * | −0.22 | −0.33 * | |
Sorting (free sort) | −0.31 | −0.15 | −0.24 | −0.37* | −0.37 * | |
Adaptive function | Social index (self-report) | −0.46 * | −0.35 | −0.19 | −0.31 | −0.43 * |
Endophenotype | Core Characteristic | Associated Functional Domains | |||
---|---|---|---|---|---|
Social | Intellect | Executive | Adaptive | ||
Socially unaware | Poor self-regulation and reciprocity in conversation | ✓ | ✓ | ✓ | ✓ |
Pedantic | Self-focused and technical in interactions | ✓ | |||
Aloof | Difficulties expressing and relating to other’s emotions | ✓ | ✓ | ✓ | |
Obsessive | Regimented approach to life and tendency to ruminate | ✓ | ✓ |
Participants with ASD | Participants without ASD | ||||
---|---|---|---|---|---|
Protocol Item | Child or Adolescent ≥ 4.5–17 yr | Adult ≥ 18 yr | Child < 13 yr | Adolescent ≥ 13–17 yr | Adult ≥ 18 yr |
ADI-R + ADOS-G or DSM-IV interview + ADOS-G | + | ± | − | − | − |
Detailed developmental, medical, psychiatric and behavioural history | + | + | + | + | + |
Family History Interview | − | + | − | − | ± |
Standardised testing of cognition and executive function a | ± | + | + | + | ± |
Questionnaires of adaptive behaviour b | + | + | + | + | ± |
Broader Autism Phenotype Interview, the Faux Pas Task, Cartoon Task and Pragmatic Rating Scale | − | ± | − | + | + |
Physical Examination | + | + | + | + | + |
High resolution molecular karyotype, Fragile X testing, metabolic investigations | + | − | − | − | − |
Unaffected | BAP | |
---|---|---|
Number of participants (female) | 11 (6) | 30 (19) |
Mean age (range) | 41.09 (18–53) | 39.50 (14–53) |
Mean BAPQ (SD) a | 2.43 (0.38) | 2.92 (0.92) |
Mean FSIQ (SD) b | 108 (14) | 111 (13) |
Mean VCI (SD) b | 106 (18) | 109 (15) |
Mean PRI (SD) b | 109 (7) | 110 (15) |
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Trevis, K.J.; Brown, N.J.; Green, C.C.; Lockhart, P.J.; Desai, T.; Vick, T.; Anderson, V.; Pua, E.P.K.; Bahlo, M.; Delatycki, M.B.; et al. Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype. Int. J. Mol. Sci. 2020, 21, 7965. https://doi.org/10.3390/ijms21217965
Trevis KJ, Brown NJ, Green CC, Lockhart PJ, Desai T, Vick T, Anderson V, Pua EPK, Bahlo M, Delatycki MB, et al. Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype. International Journal of Molecular Sciences. 2020; 21(21):7965. https://doi.org/10.3390/ijms21217965
Chicago/Turabian StyleTrevis, Krysta J., Natasha J. Brown, Cherie C. Green, Paul J. Lockhart, Tarishi Desai, Tanya Vick, Vicki Anderson, Emmanuel P. K. Pua, Melanie Bahlo, Martin B. Delatycki, and et al. 2020. "Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype" International Journal of Molecular Sciences 21, no. 21: 7965. https://doi.org/10.3390/ijms21217965