Ca p ol av ori d el la r ch eolog ia

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Ca p ol av ori d el la r ch eolog ia

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PE AM M. JR LO. UA AV. ND AU A. EN PA. IA GU N. IS R GE. AR A JE. TU AR. C OL SU. AN PJ. ES JR. E ASO C. RA GU JR. ES R ES. JR RO. AR DO.However, it is not established if this relation is of genetic origin.

Here, we applied statistical methods based on the conditional false discovery rate FDR framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits.

We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Conclusion: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci.

Still their etiologies are incompletely understood and no curative treatments exist Grande et al. Yet, epidemiological, pathophysiological, and clinical data suggest that AD and BIP could be related. A recent meta-analysis reports an odds ratio of 2.

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The risk of dementia is higher among patients with BIP compared to patients with arthritis, diabetes, and schizophrenia Kessing et al. Among patients with BIP, treatment with lithium is associated with a reduced risk of dementia Kessing et al. Among patients with AD or mild cognitive impairment, a meta-analysis of randomized controlled studies found that lithium decreased cognitive decline Matsunaga et al. There is also evidence of inflammatory processes in both conditions Goldstein et al.

Further, euthymic patients with BIP have impairments of episodic memory Torres et al. Despite several lines of evidence suggesting a relation between AD and BIP, it is not established if the conditions have a shared genetic basis. AD and BIP are in most cases complex traits, i. Genome wide association studies GWASs are the gold standard for hypothesis-free assessment of associations between complex traits and common genetic variants Corvin et al.

The power of a GWAS is a function of study sample size and the genetic architecture of the trait i. With the current sample sizes, however, the power of GWASs can be boosted by leveraging polygenic overlap between complex traits Andreassen et al.

Design: Logo by Von Glitschka, Paul Howalt

Shared genetic influences are common among complex traits Visscher et al. Statistical methods based on the conditional FDR framework can detect polygenic overlap between complex traits and utilize this polygenic overlap to increase the power to identify common genetic variants associated with each trait and jointly with two or more traits Andreassen et al.

We obtained summary statistics i. The IGAP is a two-stage study. We did not use data from stage 2 of the study since the conditional FDR method require genome-wide summary statistics which are not inflated. Informed consents were provided from all participants, or, in the case of substantial cognitive impairment, from caregivers, legal guardians, or other proxies.

The sub-studies were approved by local ethic committees.


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