Initial Genome Scan of the NIMH Genetics Initiative Bipolar Pedigrees: Chromosomes 4, 7, 9, 18, 19, 20, and 21q

✍ Scribed by Detera-Wadleigh, Sevilla D.; Badner, Judith A.; Yoshikawa, Takeo; Sanders, Alan R.; Goldin, Lynn R.; Turner, Gordon; Rollins, Denise Y.; Moses, Tracy; Guroff, Juliet J.; Kazuba, Diane; Maxwell, Mary E.; Edenberg, Howard J.; Foroud, Tatiana; Lahiri, Debomoy; Nurnberger, John I.; Stine, O. Colin; McMahon, Francis; Meyers, Deborah A.; MacKinnon, Dean; Simpson, Sylvia; McInnis, Melvin; DePaulo, J. Raymond; Rice, John; Goate, Alison; Reich, Theodore; Blehar, Mary C.; Gershon, Elliot S.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 174 KB
• Volume: 74
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(19970531)74:3<254::aid-ajmg4>3.0.co;2-q

✦ Synopsis

An initial genome scan was performed on 540 individuals from 97 families segregating bipolar disorder, collected through the National Institutes of Mental Health Genetics Initiative. We report here affected-sib-pair (ASP) data on 126 marker loci (≈68,000 genotypes) mapping to chromosomes 4, 7, 9, 18, 19, 20, and 21q, under three affection status models. Modest increases in identical-bydescent (IBD) allele sharing were found at the following loci: D4S2397 and D4S391 (P < 0.05) on 4p, D4S1647 (P < 0.05) on 4q, D7S1802 and D7S1869 (low P = 0.01) on 7p, D9S302 (P = 0.004) on 9q, and D20S604 on 20p and D20S173 on 20q ( P ≤ 0.05). In addition, five markers on 7q displayed increased IBD sharing (P = 0.046-0.002). Additional ASP analyses on chromosomes 18 and 21q marker data were performed using disease phenotype models defined previously. On chromosome 18, only D18S40 on 18p and D18S70 on 18q yielded a slight elevation in allele sharing (P = 0.02), implying that the reported linkages in these regions were not confirmed. On chromosome 21q, a cluster of markers within an ≈9 cM interval: D21S1254, D21S65, D21S1440, and D21S1255 exhibited excess allele sharing (P = 0.041-0.008). Multilocus data on overlapping marker quartets, from D21S1265 to D21S1255, which were consistent with increased IBD sharing (P < 0.01, with a low of 0.0009), overlapped a broad interval of excess allele sharing reported previously, increasing support for a susceptibility locus for bipolar disorder on 21q. Am.