Summary
Complex traits, including migraine, often aggregate in families, but
the underlying genetic architecture behind this is not well understood. The
aggregation could be explained by rare, penetrant variants that segregate
according to Mendelian inheritance or by the sufficient polygenic accumulation
of common variants, each with an individually small effect, or a combination of
the two hypotheses. In 8,319 individuals across 1,589 migraine families, we
calculated migraine polygenic risk scores (PRS) and found a significantly
higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI =
1.71–1.81, p = 1.7 × 10 −109) compared to population cases from the FINRISK
cohort (n = 1,101, OR = 1.32, 95% CI = 1.25–1.38, p = 7.2 × 10 −17). The PRS
explained 1.6% of the phenotypic variance in the population cases and 3.5% in
the familial cases (including 2.9% for migraine without aura, 5.5% for migraine
with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a
significant contribution of common polygenic variation to the familial
aggregation of migraine.
Keywords
polygenic risk score, PRS, familial aggregation, disease aggregation, migraine
families, migraine with aura, hemiplegic migraine, genome-wide association
study, GWAS
Summary
Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71–1.81, p = 1.7 × 10 −109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25–1.38, p = 7.2 × 10 −17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine.
Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71–1.81, p = 1.7 × 10 −109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25–1.38, p = 7.2 × 10 −17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine.
Keywords
polygenic risk score, PRS, familial aggregation, disease aggregation, migraine families, migraine with aura, hemiplegic migraine, genome-wide association study, GWAS
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