The female protective effect against autism spectrum disorder

Emilie M Wigdor; Daniel J Weiner; Jakob Grove; Jack M Fu; Wesley K Thompson; Caitlin E Carey; Nikolas Baya; Celia van der Merwe; Raymond K Walters; F Kyle Satterstrom; Duncan S Palmer; Anders Rosengren; Jonas Bybjerg-Grauholm; David M Hougaard; Preben Bo Mortensen; Mark J Daly; Michael E Talkowski; Stephan J Sanders; Somer L Bishop; Anders D Børglum; Elise B Robinson; iPSYCH Consortium

doi:10.1016/j.xgen.2022.100134

The female protective effect against autism spectrum disorder

Emilie M Wigdor, Daniel J Weiner, Jakob Grove, Jack M Fu, Wesley K Thompson, Caitlin E Carey, Nikolas Baya, Celia van der Merwe, Raymond K Walters, F Kyle Satterstrom, Duncan S Palmer, Anders Rosengren, Jonas Bybjerg-Grauholm, David M Hougaard, Preben Bo Mortensen, Mark J Daly, Michael E Talkowski, Stephan J Sanders, Somer L Bishop, Anders D BørglumElise B Robinson^*, iPSYCH Consortium

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

51 Citations (Scopus)

Abstract

Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10-10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10-7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD's common inherited influences.

Original language	English
Article number	100134
Journal	Cell Genomics
Volume	2
Issue	6
Number of pages	13
ISSN	2666-979X
DOIs	https://doi.org/10.1016/j.xgen.2022.100134
Publication status	Published - Jun 2022

Keywords

ASD
autism
epidemiology
female protective effect
genetics
genomics
polygenic scores
recurrent risk
sex differences

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10.1016/j.xgen.2022.100134Licence: CC BY

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Wigdor, E. M., Weiner, D. J., Grove, J., Fu, J. M., Thompson, W. K., Carey, C. E., Baya, N., van der Merwe, C., Walters, R. K., Satterstrom, F. K., Palmer, D. S., Rosengren, A., Bybjerg-Grauholm, J., Hougaard, D. M., Mortensen, P. B., Daly, M. J., Talkowski, M. E., Sanders, S. J., Bishop, S. L., ... iPSYCH Consortium (2022). The female protective effect against autism spectrum disorder. Cell Genomics, 2(6), Article 100134. https://doi.org/10.1016/j.xgen.2022.100134

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title = "The female protective effect against autism spectrum disorder",

abstract = "Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10-10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10-7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD's common inherited influences.",

keywords = "ASD, autism, epidemiology, female protective effect, genetics, genomics, polygenic scores, recurrent risk, sex differences",

author = "Wigdor, {Emilie M} and Weiner, {Daniel J} and Jakob Grove and Fu, {Jack M} and Thompson, {Wesley K} and Carey, {Caitlin E} and Nikolas Baya and {van der Merwe}, Celia and Walters, {Raymond K} and Satterstrom, {F Kyle} and Palmer, {Duncan S} and Anders Rosengren and Jonas Bybjerg-Grauholm and Hougaard, {David M} and Mortensen, {Preben Bo} and Daly, {Mark J} and Talkowski, {Michael E} and Sanders, {Stephan J} and Bishop, {Somer L} and B{\o}rglum, {Anders D} and Robinson, {Elise B} and {iPSYCH Consortium}",

note = "{\textcopyright} 2022 The Authors.",

year = "2022",

month = jun,

doi = "10.1016/j.xgen.2022.100134",

language = "English",

volume = "2",

journal = "Cell Genomics",

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Wigdor, EM, Weiner, DJ, Grove, J, Fu, JM, Thompson, WK, Carey, CE, Baya, N, van der Merwe, C, Walters, RK, Satterstrom, FK, Palmer, DS, Rosengren, A, Bybjerg-Grauholm, J, Hougaard, DM, Mortensen, PB, Daly, MJ, Talkowski, ME, Sanders, SJ, Bishop, SL, Børglum, AD, Robinson, EB & iPSYCH Consortium 2022, 'The female protective effect against autism spectrum disorder', Cell Genomics, vol. 2, no. 6, 100134. https://doi.org/10.1016/j.xgen.2022.100134

TY - JOUR

T1 - The female protective effect against autism spectrum disorder

AU - Wigdor, Emilie M

AU - Weiner, Daniel J

AU - Grove, Jakob

AU - Fu, Jack M

AU - Thompson, Wesley K

AU - Carey, Caitlin E

AU - Baya, Nikolas

AU - van der Merwe, Celia

AU - Walters, Raymond K

AU - Satterstrom, F Kyle

AU - Palmer, Duncan S

AU - Rosengren, Anders

AU - Bybjerg-Grauholm, Jonas

AU - Hougaard, David M

AU - Mortensen, Preben Bo

AU - Daly, Mark J

AU - Talkowski, Michael E

AU - Sanders, Stephan J

AU - Bishop, Somer L

AU - Børglum, Anders D

AU - Robinson, Elise B

AU - iPSYCH Consortium

PY - 2022/6

Y1 - 2022/6

N2 - Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10-10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10-7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD's common inherited influences.

AB - Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10-10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10-7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD's common inherited influences.

KW - ASD

KW - autism

KW - epidemiology

KW - female protective effect

KW - genetics

KW - genomics

KW - polygenic scores

KW - recurrent risk

KW - sex differences

U2 - 10.1016/j.xgen.2022.100134

DO - 10.1016/j.xgen.2022.100134

M3 - Journal article

C2 - 36778135

SN - 2666-979X

VL - 2

JO - Cell Genomics

JF - Cell Genomics

IS - 6

M1 - 100134

ER -

The female protective effect against autism spectrum disorder

Abstract

Keywords

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