{"id":246742,"date":"2026-11-06T10:15:50","date_gmt":"2026-11-06T16:15:50","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2026\/11\/common-mc1r-variants-and-parkinson-disease-progression"},"modified":"2026-11-06T10:15:50","modified_gmt":"2026-11-06T16:15:50","slug":"common-mc1r-variants-and-parkinson-disease-progression","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2026\/11\/common-mc1r-variants-and-parkinson-disease-progression","title":{"rendered":"Common MC1R Variants and Parkinson Disease Progression"},"content":{"rendered":"\n

This longitudinal cohort study used data from PPMI, including participants from the PD, genetic registry, and prodromal cohorts.29<\/a><\/sup> Participants carrying known pathogenic variants in SNCA<\/i> (n = 39), PRKN<\/i> (n = 9), PINK1<\/i> (n = 1), PARK7<\/i> (n = 1), and VPS35<\/i> (n = 1), as well as those without evidence of dopamine deficiency (n = 66), were excluded. Using genomewide sequencing data generated by the PPMI Genetics Core (Illumina platform processed following Genomic Analysis ToolKit Best Practices), 809 participants with PD were classified as having sporadic (n = 383) or monogenic disease (n = 426) based on LRRK2<\/i> and GBA<\/i> carrier status.29<\/a><\/sup> The sporadic cohort served as the primary analysis group. Participants within each group were then stratified by MC1R<\/i> loss-of-function carrier status (sporadic: 231 carriers and 152 noncarriers). Separately, 53 participants with prodromal PD enrolled for rapid eye movement sleep behavior disorder (clinical diagnosis by site investigator, with polysomnography where available) or hyposmia (University of Pennsylvania Smell Identification Test \u226415th age-and sex-adjusted percentile) with available genomewide sequencing data and without LRRK2<\/i> or GBA<\/i> variants were stratified into carriers (n = 34; 21 with rapid eye movement sleep behavior disorder, 13 with hyposmia) and noncarriers (n = 19; 13 with rapid eye movement sleep behavior disorder and 6 with hyposmia).<\/p>\n

MC1R<\/i> loss-of-function variants were defined as coding variants with experimentally demonstrated reductions in MC1R<\/i> function.5<\/a><\/sup>,6<\/a>,16<\/a><\/sup>,20<\/a><\/sup> Variants were further classified by penetrance: high-penetrance R variants substantially reduce MC1R<\/i> function, while low-penetrance r variants reduce function to a lesser extent.5<\/a><\/sup>,6<\/a><\/sup>\ufeff MC1R<\/i> loss-of-function carriers were further stratified by zygosity (heterozygosity [including compound heterozygosity] vs homozygosity), variant penetrance, and variant.<\/p>\n

Data were collected by PPMI between July 7, 2010, and January 1, 2026, and last accessed via the PPMI portal on February 14, 2026. Informed consent was obtained from all PPMI participants at their respective enrollment sites as part of the PPMI study protocol.<\/p>\n","protected":false},"excerpt":{"rendered":"

This longitudinal cohort study used data from PPMI, including participants from the PD, genetic registry, and prodromal cohorts.29 Participants carrying known pathogenic variants in SNCA (n = 39), PRKN (n = 9), PINK1 (n = 1), PARK7 (n = 1), and VPS35 (n = 1), as well as those without evidence of dopamine deficiency (n [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,412,47,1901],"tags":[],"class_list":["post-246742","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-genetics","category-neuroscience","category-sex"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/246742","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=246742"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/246742\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=246742"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=246742"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=246742"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}