Another report provided moderately strong support for the gene encoding the muscarinic acetylcholine receptor M2 (genetic locus CHRM2) as an AD risk locus (Wang et al. 2004). Like the ADH cluster loci and GABRA2, CHRM2 maps into a chromosomal region that was identified by an AD linkage study as being “of interest” (Reich et al. 1998). We replicated this finding (Luo et al. 2005c). There have been many other candidate gene studies in AD that we will not discuss in detail. For example, we (Luo et al. 2003) demonstrated a haplotypic association of OPRM1 (which encodes the μ opioid receptor) to the joint phenotype of AD and opioid dependence, and to AD (Zhang et al. 2006). A number of studies have also shown association of AD to the minor (G) allele of an A118G polymorphism in OPRM1, which encodes an amino acid substitution (Asn40Asp) in the extracellular portion of the μ opioid receptor. Although that polymorphism appears to be functional, there is controversy as to whether the change associated with the minor (Asp40) allele is a gain or loss of
