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Title of Journal: Hum Genet

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Abbravation: Human Genetics

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Springer-Verlag

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DOI

10.1007/bf02063629

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1432-1203

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Genebased analysis suggests association of the ni

Authors: XiangYang Lou Jennie Z Ma Thomas J Payne Joke Beuten Karen M Crew Ming D Li
Publish Date: 2006/07/28
Volume: 120, Issue: 3, Pages: 381-389
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Abstract

Based on our previously identified linkage regions for nicotine dependence ND we selected six and five single nucleotide polymorphisms SNPs in the muscarinic cholinergic receptor subtype M1 CHRM1 and nicotinic cholinergic receptor β1 CHRNB1 respectively to determine the association of the two genes with ND in a total of 2037 subjects from 602 nuclear families of either AfricanAmerican AA or EuropeanAmerican EA origin Individual SNP and/or haplotypebased analyses indicated that the CHRNB1 was significantly associated with ND which was assessed by smoking quantity SQ the Heaviness of Smoking Index HSI and the Fagerström Test for ND FTND in both ethnic samples The association of rs2302763 in the CHRNB1 was significant with adjusted SQ in the EA sample after correction for multiple testing P = 0013 Haplotype ATA formed by SNPs rs2302765 rs2302762 and rs9217 in the CHRNB1 was significantly associated with the high risk allele for all the three ND measures minimum P = 0009 0006 and 0008 for SQ HSI and FTND respectively in the AA sample while haplotype ATA formed by rs2302765 rs2302763 and rs9217 was significantly positively associated with ND minimum P = 0005 0016 and 0016 for SQ HSI and FTND respectively in the EA sample The CHRM1 exhibited significant protective associations of haplotype CCATGG formed by all six SNPs of this gene with at least one ND measure in the AA sample after Bonferroni correction minimum P = 0008 0013 and 0009 for SQ HSI and FTND respectively but no significant association was found in the EA sample The significant associations together with their location of linked region to ND suggest that the CHRNB1 and CHRM1 are likely candidates for further investigation

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