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Twin studies in bipolar disorder — MRCPsych Paper A MCQ

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ModerateGeneticsTwin studies in bipolar disorderMRCPsych Paper A

In twin studies using the same diagnostic assessment for both groups, monozygotic twins show substantially greater concordance for bipolar disorder than dizygotic twins, although monozygotic concordance remains well below 100%. Which explanation best accounts for this pattern?

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Correct answer: A — Bipolar disorder has substantial heritability, with non-genetic influences on its expression

Explanation lettering: E = shown as A · D = shown as B · B = shown as C · A = shown as D · C = shown as E

E is correct. Greater concordance in monozygotic twins, who share essentially all their inherited DNA sequence, than in dizygotic twins, who share approximately half of segregating genetic variation, supports a substantial genetic contribution to liability. Concordance remaining below 100% shows that genetic similarity does not determine the phenotype completely; non-shared environmental, developmental, epigenetic and stochastic influences may affect expression. Option A invokes a potential limitation of twin studies but does not adequately explain the established heritability estimates. Mitochondrial inheritance would predict a maternal transmission pattern, not this concordance pattern. A fully penetrant single-gene model would produce near-complete monozygotic concordance. No genetic contribution is incompatible with the consistently higher concordance among monozygotic twins.

Reference: McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Archives of General Psychiatry. 2003;60(5):497–502. https://pubmed.ncbi.nlm.nih.gov/12742871/