TY - JOUR
T1 - Insufficient Evidence for “Autism-Specific” Genes
AU - Myers, Scott M.
AU - Challman, Thomas D.
AU - Bernier, Raphael
AU - Bourgeron, Thomas
AU - Chung, Wendy K.
AU - Constantino, John N.
AU - Eichler, Evan E.
AU - Jacquemont, Sebastien
AU - Miller, David T.
AU - Mitchell, Kevin J.
AU - Zoghbi, Huda Y.
AU - Martin, Christa Lese
AU - Ledbetter, David H.
N1 - Funding Information:
We thank Hermela Shimelis for assistance with the Geisinger DBD Genes Database data and the creation of Figure 1 . This work was supported, in part, by the National Institute of Mental Health ( NIMH ) and Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health ( NIH ), under award numbers R01MH074090 , R01MH107431 , and U01MH11970510 (D.H.L., C.L.M., S.M.M.); Institut Pasteur, Université de Paris, Fondation Bettencourt-Schueller (T.B.); the Simons Foundation Autism Research Initiative (W.K.C.); the Eunice Kennedy Shriver National Institute of Child Health and Human Development award number U54 HD087011 (J.N.C.); NIH grant MH101221 (E.E.E.); and the Canadian Institute of Health Research Canada Research Chair , Canadian Institute of Health Research award number 400528 , and NIMH award number U01 MH119690-01 (S.J.). E.E.E. is an investigator of the Howard Hughes Medical Institute . D.T.M. receives an honorarium to serve on the Medical Genetics Committee of the Simons Foundation Powering Autism Research ( SPARK ) project and receives salary support from NIH grant U41 HG006834 (a Unified Clinical Genomics Database). H.Y.Z. is an investigator of the Howard Hughes Medical Institute .
Funding Information:
We thank Hermela Shimelis for assistance with the Geisinger DBD Genes Database data and the creation of Figure 1. This work was supported, in part, by the National Institute of Mental Health (NIMH) and Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health (NIH), under award numbers R01MH074090, R01MH107431, and U01MH11970510 (D.H.L. C.L.M. S.M.M.); Institut Pasteur, Université de Paris, Fondation Bettencourt-Schueller (T.B.); the Simons Foundation Autism Research Initiative (W.K.C.); the Eunice Kennedy Shriver National Institute of Child Health and Human Development award number U54 HD087011 (J.N.C.); NIH grant MH101221 (E.E.E.); and the Canadian Institute of Health Research Canada Research Chair, Canadian Institute of Health Research award number 400528, and NIMH award number U01 MH119690-01 (S.J.). E.E.E. is an investigator of the Howard Hughes Medical Institute. D.T.M. receives an honorarium to serve on the Medical Genetics Committee of the Simons Foundation Powering Autism Research (SPARK) project and receives salary support from NIH grant U41 HG006834 (a Unified Clinical Genomics Database). H.Y.Z. is an investigator of the Howard Hughes Medical Institute.
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/5/7
Y1 - 2020/5/7
N2 - Despite evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental and neuropsychiatric disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review the findings and limitations of recent efforts to identify relatively “autism-specific” genes, efforts which focus on rare variants of large effect size that are thought to account for the observed phenotypes. We present a divergent interpretation of published evidence; discuss practical and theoretical issues related to studying the relationships between rare, large-effect deleterious variants and neurodevelopmental phenotypes; and describe potential future directions of this research. We argue that there is currently insufficient evidence to establish meaningful ASD specificity of any genes based on large-effect rare-variant data.
AB - Despite evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental and neuropsychiatric disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review the findings and limitations of recent efforts to identify relatively “autism-specific” genes, efforts which focus on rare variants of large effect size that are thought to account for the observed phenotypes. We present a divergent interpretation of published evidence; discuss practical and theoretical issues related to studying the relationships between rare, large-effect deleterious variants and neurodevelopmental phenotypes; and describe potential future directions of this research. We argue that there is currently insufficient evidence to establish meaningful ASD specificity of any genes based on large-effect rare-variant data.
KW - ▪▪▪
UR - http://www.scopus.com/inward/record.url?scp=85084126275&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2020.04.004
DO - 10.1016/j.ajhg.2020.04.004
M3 - Comment/debate
C2 - 32359473
AN - SCOPUS:85084126275
SN - 0002-9297
VL - 106
SP - 587
EP - 595
JO - American journal of human genetics
JF - American journal of human genetics
IS - 5
ER -