What is the role of the major affective disorder (MAFD) loci in the pathophysiology of bipolar affective disorder (manic-depressive illness)?

Updated: May 30, 2019
  • Author: Stephen Soreff, MD; Chief Editor: Glen L Xiong, MD  more...
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MAFD1 is located at 18p and was originally described in a group of 22 patients with bipolar disorder. [8] MAFD2 is located at Xq28 and, as such, is associated with an X-linked inheritance pattern. The notion of an X-linked form of bipolar disorder is not a new one, and at least one paper from the pregenetic era discusses this very possibility. [9] MAFD3 is located at 21q22.13, and the association appears to be with the TRPM2 gene. [10, 11] MAFD4 is located at 16p12 and has been associated with susceptibility to bipolar disease in a cohort of 41 Finnish families. [12]

MAFD5 is located at 2q22-q24, and MAFD6 is located at 6q23-24. Interestingly, evidence suggests a strong interaction between genes located in these 2 regions. It has been concluded that the candidate gene in the MAFD5 locus shows epistatic interaction with the MAFD6 risk locus. [13] MAFD7 is located at 22q12.1 and was detected using microsatellite markers in a North American population; a large region on 22q12 was associated with bipolar disorder in this study. [14] Further study in this region showed a polymorphism in the promoter region of the XBP1 gene, which also showed susceptibility to bipolar disorder in a Japanese cohort. [15] XBP1 appears to be involved mainly in immune system function; thus,its influence on the susceptibility of bipolar disorder is not understood.

MAFD8 is located at 10q21, and its discovery is the result of a large analysis of over 1.8 million variants in 4387 cases of bipolar disorder. [16] The association in this study appears to be with the ANK3 gene, which is a gene of marked interest and is therefore discussed at length below. [16] MAFD9 is located at 12p13.3, and its discovery is the result of the same large analysis as MAFD8. The association in this study appears to be with the CACNA1C gene. [16] Like ANK3, it remains a gene of interest [17] and is also mentioned below.

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