Multimarkerhaplotypes within the serotonin transporter gene suggest evidence of an association with bipolar disorder

Previously we obtained modest linkage evidence implicating 17q11.1-12 in bi polar disorder. A modified genome screen, based on gene-rich regions, on a collection of Irish sib-pair nuclear families revealed excess allele sharin g at markers flanking the gene encoding the serotonin transporter (5-HTT; h SERT), Here we describe a study designed to combine the advantages of famil y-based association studies with the consideration of multiple polymorphic markers within a candidate gene. Ninety-two Irish families, with a total of 106 proband-parent trios, have been genotyped for 3 previously known polym orphisms within hSERT (5HTTLPR, intron 2 VNTR, and 3' UTR G/T). Data from t wo and three polymorphic marker haplotypes revealed a number of marker comb inations that showed evidence supportive of association; the most significa nt being for polymorphisms 5-HTTLPR and 3' UTR GPT (global chi (2), 12.91, df 3, P = 0.005), In addition, modest evidence of association also was obse rved for 5-HTTLPR alone, (C) 2000 Wiley-Liss,Inc.