{"id":105493,"date":"2022-06-30T07:00:58","date_gmt":"2022-06-30T11:00:58","guid":{"rendered":"http:\/\/www.bumc.bu.edu\/busm\/?p=105493"},"modified":"2022-06-29T14:16:14","modified_gmt":"2022-06-29T18:16:14","slug":"novel-gene-for-alzheimers-disease-in-women-identified","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/camed\/2022\/06\/30\/novel-gene-for-alzheimers-disease-in-women-identified\/","title":{"rendered":"Novel Gene for Alzheimer\u2019s Disease in Women Identified"},"content":{"rendered":"

Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia, affecting more than 5.8 million individuals in the U.S. Scientists have discovered some genetic variants that increase the risk for developing Alzheimer\u2019s; the most well-known of these for people over the age of 65 is the APOE <\/em>\u03b54 allele. Approximately 60 percent of people from European ancestry with Alzheimer\u2019s carry this genetic variant, compared to just 26 percent of the general population, implying that other genes contribute to the genetic makeup of the disease.<\/p>\n

In a new study published this week in Alzheimer\u2019s Disease & Dementia: The Journal of the Alzheimer’s Association<\/em><\/a>, researchers at the University of Chicago and Boston University School of Medicine (BUSM) have identified a new gene called MGMT<\/em> that increases the risk of Alzheimer\u2019s in women.<\/p>\n

The researchers conducted a genome-wide association study (GWAS) for Alzheimer\u2019s in two independent datasets using different methods. One approach focused on dementia in a large extended family of Hutterites, a founder population of central European ancestry who settled in the mid-west region of the country. Hutterites are often studied for genetic determinants of disease because they have a relatively small gene pool due to their isolated, insular culture. In this study, the individuals with Alzheimer\u2019s were all women. The second approach, predicated on evidence suggesting a link between Alzheimer\u2019s and breast cancer, analyzed genetic data from a national group of 10,340 women who lacked APOE<\/em> \u03b54. In both datasets, MGMT<\/em> was significantly associated with developing AD.<\/p>\n

\"Headshot\u201cThis is one of a few and perhaps the strongest associations of a genetic risk factor for Alzheimer\u2019s that is specific to women,\u201d said Lindsay Farrer, PhD, chief of biomedical genetics at BUSM and a senior author of the study. \u201cThis finding is particularly robust because it was discovered independently in two distinct populations using different approaches. While the finding in the large dataset was most pronounced in women who don\u2019t have APOE<\/em> \u03b54, the Hutterite sample was too small to evaluate this pattern with any certainty.\u201d<\/p>\n

The researchers then further evaluated MGMT<\/em> using multiple types of molecular data and other AD-related traits derived from human brain tissue. After thorough analysis, they found that that epigenetically regulated gene expression (i.e., one of the ways cells control gene activity without changing the DNA sequence)<\/span> of MGMT<\/em>, which has a role in repairing DNA damage, is significantly associated with the development of the hallmark AD proteins, amyloid-\u03b2 and tau, especially in women.<\/p>\n

\u201cThis study highlighted the value of founder populations for genetic mapping studies of diseases like Alzheimer\u2019s,\u201d said Carole Ober, PhD, Chair of Human Genetics at UChicago and a senior author of the study. \u201cThe relatively uniform environment and reduced genetic variation in Hutterites increases our power to find associations in smaller sample sizes than required for studies in the general population. The validation of our findings in the larger dataset used by the Boston University group was enormously gratifying and ultimately led to supportive epigenetic mechanisms that connected both sets of GWAS results to the MGMT <\/em>gene.\u201d<\/p>\n

According to the researchers, this study demonstrates the importance of searching for genetic risk factors for AD that may be specific to one gender. Further studies are needed to understand why MGMT <\/em>influences AD risk greater in women than men.<\/p>\n","protected":false},"excerpt":{"rendered":"

Findings may help explain why Alzheimer’s is more prevalent in women than men.<\/p>\n","protected":false},"author":903,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[90],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/105493"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/users\/903"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/comments?post=105493"}],"version-history":[{"count":4,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/105493\/revisions"}],"predecessor-version":[{"id":105507,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/posts\/105493\/revisions\/105507"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/media?parent=105493"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/categories?post=105493"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/camed\/wp-json\/wp\/v2\/tags?post=105493"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}