02910nas a2200265   4500008004100000022001400041245011100055210006900166260001600235520208900251100002402340700001502364700002002379700001502399700001502414700002302429700002102452700002502473700002302498700002102521700002102542700001902563700002602582856003602608       2017                        eng d  a1873-681500aHidden heterogeneity in Alzheimer's disease: Insights from genetic association studies and other analyses.0 aHidden heterogeneity in Alzheimers disease Insights from genetic  c2017 Oct 263 a<p>Despite evident success in clarifying many important features of Alzheimer's disease (AD) the efficient methods of its prevention and treatment are not yet available. The reasons are likely to be the fact that AD is a multifactorial and heterogeneous health disorder with multiple alternative pathways of disease development and progression. The availability of genetic data on individuals participated in longitudinal studies of aging health and longevity, as well as on participants of cross-sectional case-control studies allow for investigating genetic and non-genetic connections with AD and to link the results of these analyses with research findings obtained in clinical, experimental, and molecular biological studies of this health disorder. The objective of this paper is to perform GWAS of AD in several study populations and investigate possible roles of detected genetic factors in developing AD hallmarks and in other health disorders. The data collected in the Framingham Heart Study (FHS), Cardiovascular Health Study (CHS), Health and Retirement Study (HRS) and Late Onset Alzheimer's Disease Family Study (LOADFS) were used in these analyses. The logistic regression and Cox's regression were used as statistical models in GWAS. The results of analyses confirmed strong associations of genetic variants from well-known genes APOE, TOMM40, PVRL2 (NECTIN2), and APOC1 with AD. Possible roles of these genes in pathological mechanisms resulting in development of hallmarks of AD are described. Many genes whose connection with AD was detected in other studies showed nominally significant associations with this health disorder in our study. The evidence on genetic connections between AD and vulnerability to infection, as well as between AD and other health disorders, such as cancer and type 2 diabetes, were investigated. The progress in uncovering hidden heterogeneity in AD would be substantially facilitated if common mechanisms involved in development of AD, its hallmarks, and AD related chronic conditions were investigated in their mutual connection.</p>1 aYashin, Anatoliy, I1 aFang, Fang1 aKovtun, Mikhail1 aWu, Deqing1 aDuan, Matt1 aArbeev, Konstantin1 aAkushevich, Igor1 aKulminski, Alexander1 aCulminskaya, Irina1 aZhbannikov, Ilya1 aYashkin, Arseniy1 aStallard, Eric1 aUkraintseva, Svetlana  uhttps://chs-nhlbi.org/node/7598