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 bipolar disorder. A modified genome screen, based on gene-rich regions, on a collection of Irish sib-pair nuclear families revealed excess allele sharing at markers flanking the gene encoding the serotonin transporter (5-HTT; hSERT). Here we describe a study designed to combine the advantages of family-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 polymorphisms within hSERT (5-HTTLPR, intron 2 VNTR, and 3' UTR G/T). Data from two and three polymorphic marker haplotypes revealed a number of marker combinations that showed evidence supportive of association; the most significant being for polymorphisms 5-HTTLPR and 3' UTR G/T (global chi(2), 12.91, df 3, P = 0.005). In addition, modest evidence of association also was observed for 5-HTTLPR alone. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:845-849, 2000.
Mynett-Johnson
L
L
Department of Genetics, Smurfit Institute, Trinity College, Dublin, Ireland. lmjhnson@tcd.ie
Kealey
C
C
Claffey
E
E
Curtis
D
D
Bouchier-Hayes
L
L
Powell
C
C
McKeon
P
P
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA