Linkage Disequilibrium

Publication Title: 
Age (Dordrecht, Netherlands)

Longevity phenotype in humans results from the influence of environmental and genetic factors. Few gene polymorphisms have been identified so far with a modest effect on lifespan leaving room for the search of other players in the longevity game. It has been recently demonstrated that targeted disruption of the mouse homolog of the human angiotensin II type 1 receptor (AT1R) gene (AGTR1) translates into marked prolongation of animal lifespan (Benigni et al., J Clin Invest 119(3):524-530, 2009).

Author(s): 
Benigni, Ariela
Orisio, Silvia
Noris, Marina
Iatropoulos, Paraskevas
Castaldi, Davide
Kamide, Kei
Rakugi, Hiromi
Arai, Yasumichi
Todeschini, Marta
Ogliari, Giulia
Imai, Enyu
Gondo, Yasuyuki
Hirose, Nobuyoshi
Mari, Daniela
Remuzzi, Giuseppe
Publication Title: 
Age (Dordrecht, Netherlands)

Longevity phenotype in humans results from the influence of environmental and genetic factors. Few gene polymorphisms have been identified so far with a modest effect on lifespan leaving room for the search of other players in the longevity game. It has been recently demonstrated that targeted disruption of the mouse homolog of the human angiotensin II type 1 receptor (AT1R) gene (AGTR1) translates into marked prolongation of animal lifespan (Benigni et al., J Clin Invest 119(3):524-530, 2009).

Author(s): 
Benigni, Ariela
Orisio, Silvia
Noris, Marina
Iatropoulos, Paraskevas
Castaldi, Davide
Kamide, Kei
Rakugi, Hiromi
Arai, Yasumichi
Todeschini, Marta
Ogliari, Giulia
Imai, Enyu
Gondo, Yasuyuki
Hirose, Nobuyoshi
Mari, Daniela
Remuzzi, Giuseppe
Publication Title: 
Aging Cell

?-adrenoceptors are the common pharmacological targets for the treatment of cardiovascular diseases and asthma. Genetic modifications of ?-adrenergic system in engineered mice affect their lifespan. Here, we tested whether genes encoding for key components of the ?-adrenergic signaling pathway are associated with human longevity. We performed a 10-year follow-up study of the Chinese longitudinal healthy longevity survey. The Han Chinese population in this study consisted of 963 long-lived and 1028 geography-matched young individuals.

Author(s): 
Zhao, Ling
Yang, Fan
Xu, Ke
Cao, Huiqing
Zheng, Gu-Yan
Zhang, Yan
Li, Jianxin
Cui, Hanbin
Chen, Xiaomin
Zhu, Zhiming
He, Hongbo
Mo, Xianming
Kennedy, Brian K.
Suh, Yousin
Zeng, Yi
Tian, Xiao-Li
Publication Title: 
PloS One

Cytosine-5 methylation within CpG dinucleotides is a potentially important mechanism of epigenetic influence on human traits and disease. In addition to influences of age and gender, genetic control of DNA methylation levels has recently been described. We used whole blood genomic DNA in a twin set (23 MZ twin-pairs and 23 DZ twin-pairs, N = 92) as well as healthy controls (N = 96) to investigate heritability and relationship with age and gender of selected DNA methylation profiles using readily commercially available GoldenGate bead array technology.

Author(s): 
Boks, Marco P.
Derks, Eske M.
Weisenberger, Daniel J.
Strengman, Erik
Janson, Esther
Sommer, Iris E.
Kahn, RenÈ S.
Ophoff, Roel A.
Publication Title: 
Brain, Behavior, and Immunity

Past analyses examining the relationship between genetic variation in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and psychiatric disorders have provided mixed and largely inconclusive findings. MTHFR is involved in the one-carbon metabolic pathway which is essential for DNA biosynthesis and the epigenetic process of DNA methylation.

Author(s): 
Peerbooms, Odette L. J.
van Os, Jim
Drukker, Marjan
Kenis, Gunter
Hoogveld, Loes
MTHFR in Psychiatry Group
De Hert, Marc
Delespaul, Philippe
van Winkel, Ruud
Rutten, Bart P. F.
Publication Title: 
Journal of Psychiatric Research

Common variants of the FK506 binding protein 5 (FKBP5) gene are implicated in psychotic and other disorders, via their role in regulating glucocorticoid receptor (GR) receptor sensitivity and effects on the broader function of the HPA system in response to stress.

Author(s): 
Green, Melissa J.
Raudino, Alessandra
Cairns, Murray J.
Wu, Jingqin
Tooney, Paul A.
Scott, Rodney J.
Carr, Vaughan J.
Australian Schizophrenia Research Bank
Publication Title: 
Nature Communications

DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the 'epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 ◊ 10(-8)) SNPs in two loci: 2p22.1 (inside gene DHX57) and 16p13.3 near gene MLST8 (a subunit of mTOR complex 1 and 2). We find that the SNP in 16p13.3 has a cis-acting effect on the expression levels of MLST8 (P=6.9 ◊ 10(-18)) in most brain regions. In cerebellar samples, the SNP in 2p22.1 has a cis-effect on DHX57 (P=4.4 ◊ 10(-5)).

Author(s): 
Lu, Ake T.
Hannon, Eilis
Levine, Morgan E.
Hao, Ke
Crimmins, Eileen M.
Lunnon, Katie
Kozlenkov, Alexey
Mill, Jonathan
Dracheva, Stella
Horvath, Steve
Publication Title: 
Theoretical Population Biology

We analyse the evolution of the assortment of encounters through active choice of companions among individuals that interact cooperatively in a situation of mutual benefit. Using a simple mathematical model, we show that mutual benefit can favour the evolution of a preference to interact with individuals that are similar to themselves with respect to an arbitrary tag even when both the preference and the tag depend on two independent and unlinked genes.

Author(s): 
Castro, Laureano
Toro, Miguel A.
Publication Title: 
The American Naturalist

Strong reciprocity, defined as a predisposition to help others and to punish those that are not helping, has been proposed as a potent force leading to the evolution of cooperation and altruism. However, the conditions under which strong reciprocity might be favored are not clear. Here we investigate the selective pressure on strong reciprocity by letting both limited dispersal (i.e., spatial structure) and recombination between helping and punishment jointly determine the evolutionary dynamics of strong reciprocity.

Author(s): 
Lehmann, Laurent
Rousset, FranÁois
Roze, Denis
Keller, Laurent
Publication Title: 
Statistics in Medicine

The analysis of data from matched pairs binary experiments, often performed with McNemar's test, presents a unique experimental design challenge in dealing with the effect of the discordance probability, p. Most approaches for determining size and power use point estimates or maximization, but this fails to account for the considerable variability across values of the nuisance parameter that occur for all common tests.

Author(s): 
Lennox, Kristin P.
Sherman, Michael

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