Genetic and environmental influences on major recurrent headaches

<p>The major recurrent headaches are migraine and tension-type headache. The aim of this thesis is to characterize the main genetic and environmental architecture of these idiopathic conditions of episodic cranial pain using the Swedish Twin Registry.</p><p>Recurrent headaches were examined in a nationwide cohort of 8 to 9-years-old twins through questionnaires sent to their parents (Paper 1). The prevalence of recurrent headaches was 13.7% (N=2,078 twins) and the heritability 70% (95%CI: 54, 82%) with no differences between the sexes. Further analyses disclosed phenotype heterogeneity, a genetic liability to migraine (88%, 95%CI: 67, 97%) and no genetic effects on tension-type headache.</p><p>In paper II, the prevalence of severe disabling recurrent headache during the latest years among twins aged 15-47 years (N=25,212) was 10.7% with double the risk of women compared to men (OR=2.1, 95%CI: 1.9, 2.2). Among headache sufferers, 48% of women and 32% of men had migraine headache (chi2 =53.89, P<0.0001) and these proportions increased with increasing age. A significant variation in heritability of migraine headache across age groups ranging from 91% (15-20 years) to 37% (41-47 years) was detected in women (chi2 =20.29, P<0.025). This variation was explained by less environmental variance in adolescents than in adults.</p><p>In a twin-adoption study of 314 pairs reared apart and 364 pairs matched control pairs reared together (Paper III), variance decomposition of lifetime migraine as assessed at ages 42-81 years revealed essentially the same results as those of the classical reared together design; rearing effects have no major importance and genetic variance is not confounded with specific environments of monozygotic twins.</p><p>The SALT Headache study (Papers IV-VI) encompassed assessment of lifetime recurrent headaches among twins aged 41-64 years (N=31,192) and subsequent diagnosis of migraine and tension-type headache in line with the International Headache Society (If IS) criteria using lay telephone interviews. Among sufferers of recurrent headaches (lifetime prevalence=26.1%), respectively, 59% (strict criteria) and 87% (liberal criteria) were diagnosed with migraine, tension-type headache, or both. The female-to-male ratio was above two for migraine and below two for tension-type headache. The heritability was 44% (95%CI: 35,52%) for strict migraine and 22% (95%CI: 12, 32%) for strict tension-type headache; genetic effects were mainly non-additive, heritability of tension-type headache differed between men and women (0 versus 30%; chi2 =7.08, P<0.05), and no conclusive relationship between migraine and tension-type headache was found. The heritability of varying definitions of migraine ranged from 52% (95%Cl: 46, 57%) for self-report migraine with other recurrent headaches added to the IHS core phenotype to 37% (95%CI: 30, 44%) for self-report migraine without other recurrent headaches added to the IHS core.</p><p>In conclusion, recurrent headache is a heterogeneous syndrome, where migraine is an intermediate heritable phenotype and tension-type headache a less heritable phenotype. Genetic variance of migraine is largely non-additive and stable across birth cohorts. Environment modulates manifestation of migraine mainly during adulthood whereas environmental influences on tension-type headache prevail in youth as well. Variation in the threshold of migraine affects the heritability.</p><h3>List of scientific papers</h3><p>I. Svensson DA, Larsson B, Bille B, Lichtenstein P (1999). "Genetic and environmental influences on recurrent headaches in eight to nine-year-old twins. " Cephalalgia 19(10): 866-72 <br><a href="https://pubmed.ncbi.nlm.nih.gov/10668105">https://pubmed.ncbi.nlm.nih.gov/10668105</a><br><br></p><p>II. Svensson DA, Larsson B, Waldenlind E, Pedersen NL (2002). "Genetic and environmental influences on expression of recurrent headache as a function of the reporting age in twins. " Twin Res 5(4): 277-86 <br><a href="https://pubmed.ncbi.nlm.nih.gov/12217234">https://pubmed.ncbi.nlm.nih.gov/12217234</a><br><br></p><p>III. Svensson DA, Larsson B, Waldenlind E, Pedersen NL (2003). "Shared rearing environment in migraine: results from twins reared apart and twins reared together. " Headache 43(3): 235-44 <br><a href="https://pubmed.ncbi.nlm.nih.gov/12603642">https://pubmed.ncbi.nlm.nih.gov/12603642</a><br><br></p><p>IV. Svensson DA, Waldenlind E, Ekbom K, Pedersen NL (2004). "Heritability of migrane as a function of definition." (Submitted)</p><p>V. Svensson DA, Ekbom K, Pedersen NL, Waldenlind E (2004). "A population-based twin study of migrane and yension-type headache: The lifetime occurrence." (Manuscript)</p><p>VI. Svensson DA, Ekbom K, Pedersen NL, Waldenlind E (2004). "A population-based twin study of migraine and tension-type headache: The importance of genes and the environment." (Manuscript)</p>