Individual common variants exert weak effects on the risk for autism spectrum disorders

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Proje...

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Main Authors:	Anney, R., Klei, L., Pinto, D., Almeida, J., Bacchelli, E., Baird, G., Bolshakova, N., Bölte, Sven, Bolton, P., Bourgeron, T., Brennan, S., Brian, J., Casey, J., Conroy, J., Correia, C., Corsello, C., Crawford, E., De jonge, M., Delorme, R., Duketis, E., Duque, F., Estes, A., Farrar, P., Fernandez, B., Folstein, S., Fombonne, E., Gilbert, J., Gillberg, C., Glessner, J., Green, A., Green, J., Guter, S., Heron, E., Holt, R., Howe, J., Hughes, G., Hus, V., Igliozzi, R., Jacob, S., Kenny, G., Kim, C., Kolevzon, A., Kustanovich, V., Lajonchere, C., Lamb, J., Law-Smith, M., Leboyer, M., Le couteur, A., Leventhal, B., Liu, X., Lombard, F., Lord, C., Lotspeich, L., Lund, S., Magalhaes, T., Mantoulan, C., McDougle, C., Melhem, N., Merikangas, A., Minshew, N., Mirza, G., Munson, J., Noakes, C., Nygren, G., Papanikolaou, K., Pagnamenta, A., Parrini, B., Paton, T., Pickles, A., Posey, D., Poustka, F., Ragoussis, J., Regan, R., Roberts, W., Roeder, K., Roge, B., Rutter, M., Schlitt, S., Shah, N., Sheffield, V., Soorya, L., Sousa, I., Stoppioni, V., Sykes, N., Tancredi, R., Thompson, A., Thomson, S., Tryfon, A., Tsiantis, J., Van Engeland, H., Vincent, J., Volkmar, F., Vorstman, J.
Format:	Journal Article
Published:	Oxford University Press 2012
Online Access:	http://hdl.handle.net/20.500.11937/59311

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author	Anney, R. Klei, L. Pinto, D. Almeida, J. Bacchelli, E. Baird, G. Bolshakova, N. Bölte, Sven Bolton, P. Bourgeron, T. Brennan, S. Brian, J. Casey, J. Conroy, J. Correia, C. Corsello, C. Crawford, E. De jonge, M. Delorme, R. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B. Folstein, S. Fombonne, E. Gilbert, J. Gillberg, C. Glessner, J. Green, A. Green, J. Guter, S. Heron, E. Holt, R. Howe, J. Hughes, G. Hus, V. Igliozzi, R. Jacob, S. Kenny, G. Kim, C. Kolevzon, A. Kustanovich, V. Lajonchere, C. Lamb, J. Law-Smith, M. Leboyer, M. Le couteur, A. Leventhal, B. Liu, X. Lombard, F. Lord, C. Lotspeich, L. Lund, S. Magalhaes, T. Mantoulan, C. McDougle, C. Melhem, N. Merikangas, A. Minshew, N. Mirza, G. Munson, J. Noakes, C. Nygren, G. Papanikolaou, K. Pagnamenta, A. Parrini, B. Paton, T. Pickles, A. Posey, D. Poustka, F. Ragoussis, J. Regan, R. Roberts, W. Roeder, K. Roge, B. Rutter, M. Schlitt, S. Shah, N. Sheffield, V. Soorya, L. Sousa, I. Stoppioni, V. Sykes, N. Tancredi, R. Thompson, A. Thomson, S. Tryfon, A. Tsiantis, J. Van Engeland, H. Vincent, J. Volkmar, F. Vorstman, J.
author_facet	Anney, R. Klei, L. Pinto, D. Almeida, J. Bacchelli, E. Baird, G. Bolshakova, N. Bölte, Sven Bolton, P. Bourgeron, T. Brennan, S. Brian, J. Casey, J. Conroy, J. Correia, C. Corsello, C. Crawford, E. De jonge, M. Delorme, R. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B. Folstein, S. Fombonne, E. Gilbert, J. Gillberg, C. Glessner, J. Green, A. Green, J. Guter, S. Heron, E. Holt, R. Howe, J. Hughes, G. Hus, V. Igliozzi, R. Jacob, S. Kenny, G. Kim, C. Kolevzon, A. Kustanovich, V. Lajonchere, C. Lamb, J. Law-Smith, M. Leboyer, M. Le couteur, A. Leventhal, B. Liu, X. Lombard, F. Lord, C. Lotspeich, L. Lund, S. Magalhaes, T. Mantoulan, C. McDougle, C. Melhem, N. Merikangas, A. Minshew, N. Mirza, G. Munson, J. Noakes, C. Nygren, G. Papanikolaou, K. Pagnamenta, A. Parrini, B. Paton, T. Pickles, A. Posey, D. Poustka, F. Ragoussis, J. Regan, R. Roberts, W. Roeder, K. Roge, B. Rutter, M. Schlitt, S. Shah, N. Sheffield, V. Soorya, L. Sousa, I. Stoppioni, V. Sykes, N. Tancredi, R. Thompson, A. Thomson, S. Tryfon, A. Tsiantis, J. Van Engeland, H. Vincent, J. Volkmar, F. Vorstman, J.
author_sort	Anney, R.
building	Curtin Institutional Repository
collection	Online Access
description	While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm < 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
first_indexed	2025-11-14T10:15:53Z
format	Journal Article
id	curtin-20.500.11937-59311
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T10:15:53Z
publishDate	2012
publisher	Oxford University Press
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-593112023-02-22T06:24:19Z Individual common variants exert weak effects on the risk for autism spectrum disorders Anney, R. Klei, L. Pinto, D. Almeida, J. Bacchelli, E. Baird, G. Bolshakova, N. Bölte, Sven Bolton, P. Bourgeron, T. Brennan, S. Brian, J. Casey, J. Conroy, J. Correia, C. Corsello, C. Crawford, E. De jonge, M. Delorme, R. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B. Folstein, S. Fombonne, E. Gilbert, J. Gillberg, C. Glessner, J. Green, A. Green, J. Guter, S. Heron, E. Holt, R. Howe, J. Hughes, G. Hus, V. Igliozzi, R. Jacob, S. Kenny, G. Kim, C. Kolevzon, A. Kustanovich, V. Lajonchere, C. Lamb, J. Law-Smith, M. Leboyer, M. Le couteur, A. Leventhal, B. Liu, X. Lombard, F. Lord, C. Lotspeich, L. Lund, S. Magalhaes, T. Mantoulan, C. McDougle, C. Melhem, N. Merikangas, A. Minshew, N. Mirza, G. Munson, J. Noakes, C. Nygren, G. Papanikolaou, K. Pagnamenta, A. Parrini, B. Paton, T. Pickles, A. Posey, D. Poustka, F. Ragoussis, J. Regan, R. Roberts, W. Roeder, K. Roge, B. Rutter, M. Schlitt, S. Shah, N. Sheffield, V. Soorya, L. Sousa, I. Stoppioni, V. Sykes, N. Tancredi, R. Thompson, A. Thomson, S. Tryfon, A. Tsiantis, J. Van Engeland, H. Vincent, J. Volkmar, F. Vorstman, J. While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm < 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest. 2012 Journal Article http://hdl.handle.net/20.500.11937/59311 10.1093/hmg/dds301 Oxford University Press unknown
spellingShingle	Anney, R. Klei, L. Pinto, D. Almeida, J. Bacchelli, E. Baird, G. Bolshakova, N. Bölte, Sven Bolton, P. Bourgeron, T. Brennan, S. Brian, J. Casey, J. Conroy, J. Correia, C. Corsello, C. Crawford, E. De jonge, M. Delorme, R. Duketis, E. Duque, F. Estes, A. Farrar, P. Fernandez, B. Folstein, S. Fombonne, E. Gilbert, J. Gillberg, C. Glessner, J. Green, A. Green, J. Guter, S. Heron, E. Holt, R. Howe, J. Hughes, G. Hus, V. Igliozzi, R. Jacob, S. Kenny, G. Kim, C. Kolevzon, A. Kustanovich, V. Lajonchere, C. Lamb, J. Law-Smith, M. Leboyer, M. Le couteur, A. Leventhal, B. Liu, X. Lombard, F. Lord, C. Lotspeich, L. Lund, S. Magalhaes, T. Mantoulan, C. McDougle, C. Melhem, N. Merikangas, A. Minshew, N. Mirza, G. Munson, J. Noakes, C. Nygren, G. Papanikolaou, K. Pagnamenta, A. Parrini, B. Paton, T. Pickles, A. Posey, D. Poustka, F. Ragoussis, J. Regan, R. Roberts, W. Roeder, K. Roge, B. Rutter, M. Schlitt, S. Shah, N. Sheffield, V. Soorya, L. Sousa, I. Stoppioni, V. Sykes, N. Tancredi, R. Thompson, A. Thomson, S. Tryfon, A. Tsiantis, J. Van Engeland, H. Vincent, J. Volkmar, F. Vorstman, J. Individual common variants exert weak effects on the risk for autism spectrum disorders
title	Individual common variants exert weak effects on the risk for autism spectrum disorders
title_full	Individual common variants exert weak effects on the risk for autism spectrum disorders
title_fullStr	Individual common variants exert weak effects on the risk for autism spectrum disorders
title_full_unstemmed	Individual common variants exert weak effects on the risk for autism spectrum disorders
title_short	Individual common variants exert weak effects on the risk for autism spectrum disorders
title_sort	individual common variants exert weak effects on the risk for autism spectrum disorders
url	http://hdl.handle.net/20.500.11937/59311

Individual common variants exert weak effects on the risk for autism spectrum disorders

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