A genome-wide linkage and association scan reveals novel loci for autism

Research output: Contribution to journalArticle

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A genome-wide linkage and association scan reveals novel loci for autism. / Laren, LA; Arking, DE; Daly, M; Wittemeyer, Kerstin; Chakravarti, A; The Gene Discovery Project of Johns Hopkins and Autism Consortium.

In: Nature, Vol. 461, No. 7265, 08.10.2009, p. 802-808.

Research output: Contribution to journalArticle

Harvard

Laren, LA, Arking, DE, Daly, M, Wittemeyer, K, Chakravarti, A & The Gene Discovery Project of Johns Hopkins and Autism Consortium 2009, 'A genome-wide linkage and association scan reveals novel loci for autism', Nature, vol. 461, no. 7265, pp. 802-808. https://doi.org/10.1038/nature08490

APA

Laren, LA., Arking, DE., Daly, M., Wittemeyer, K., Chakravarti, A., & The Gene Discovery Project of Johns Hopkins and Autism Consortium (2009). A genome-wide linkage and association scan reveals novel loci for autism. Nature, 461(7265), 802-808. https://doi.org/10.1038/nature08490

Vancouver

Laren LA, Arking DE, Daly M, Wittemeyer K, Chakravarti A, The Gene Discovery Project of Johns Hopkins and Autism Consortium. A genome-wide linkage and association scan reveals novel loci for autism. Nature. 2009 Oct 8;461(7265):802-808. https://doi.org/10.1038/nature08490

Author

Laren, LA ; Arking, DE ; Daly, M ; Wittemeyer, Kerstin ; Chakravarti, A ; The Gene Discovery Project of Johns Hopkins and Autism Consortium. / A genome-wide linkage and association scan reveals novel loci for autism. In: Nature. 2009 ; Vol. 461, No. 7265. pp. 802-808.

Bibtex

@article{684b8bea8edf4a28b7a1c583fa898079,
title = "A genome-wide linkage and association scan reveals novel loci for autism",
abstract = "Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.",
author = "LA Laren and DE Arking and M Daly and Kerstin Wittemeyer and A Chakravarti and {The Gene Discovery Project of Johns Hopkins and Autism Consortium}",
year = "2009",
month = oct,
day = "8",
doi = "10.1038/nature08490",
language = "English",
volume = "461",
pages = "802--808",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7265",

}

RIS

TY - JOUR

T1 - A genome-wide linkage and association scan reveals novel loci for autism

AU - Laren, LA

AU - Arking, DE

AU - Daly, M

AU - Wittemeyer, Kerstin

AU - Chakravarti, A

AU - The Gene Discovery Project of Johns Hopkins and Autism Consortium

PY - 2009/10/8

Y1 - 2009/10/8

N2 - Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

AB - Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

U2 - 10.1038/nature08490

DO - 10.1038/nature08490

M3 - Article

C2 - 19812673

VL - 461

SP - 802

EP - 808

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7265

ER -