1] Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands  Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
The adult form of attention deficit/hyperactivity disorder (aADHD) has a prevalence of up to 5% and is the most severe long-term outcome of this common neurodevelopmental disorder. Family studies in clinical samples suggest an increased familial liability for aADHD compared with childhood ADHD (cADHD), whereas twin studies based on self-rated symptoms in adult population samples show moderate heritability estimates of 30-40%. However, using multiple sources of information, the heritability of clinically diagnosed aADHD and cADHD is very similar. Results of candidate gene as well as genome-wide molecular genetic studies in aADHD samples implicate some of the same genes involved in ADHD in children, although in some cases different alleles and different genes may be responsible for adult versus childhood ADHD. Linkage studies have been successful in identifying loci for aADHD and led to the identification of LPHN3 and CDH13 as novel genes associated with ADHD across the lifespan. In addition, studies of rare genetic variants have identified probable causative mutations for aADHD. Use of endophenotypes based on neuropsychology and neuroimaging, as well as next-generation genome analysis and improved statistical and bioinformatic analysis methods hold the promise of identifying additional genetic variants involved in disease etiology. Large, international collaborations have paved the way for well-powered studies. Progress in identifying aADHD risk genes may provide us with tools for the prediction of disease progression in the clinic and better treatment, and ultimately may help to prevent persistence of ADHD into adulthood.
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"In our gene-based and gene-complex evaluation, we have examined childhood ADHD only. However, slightly different genetic risk factors may be associated with the persistent and remitting forms of this disorder [Franke et al., 2011]. Similarly, epistasis has been tested in our Norwegian sample of adult ADHD only and its further exploration in childhood ADHD (as well as other neuropsychiatric disorders) is warranted. "
"Neuropsychiatric Genetics suggest strong candidate genes for ADHD [Genro et al., 2010; Franke et al., 2012]. The most frequently reported and replicated associations with dopaminergic gene variants are for the genes encoding the D4 receptor (DRD4) and the dopamine transporter (DAT1 or SLC6A3). "
"ploPS , F ST and LSBL as a strong selection signal ( Table 2 ; Figure S3 ) . CDH13 encod - ing a GPI - anchored member of the cadherin superfamily , has been associated with atherosclerosis protection ( UCSC Genome Browser ; Lee et al . 2013 ; Takeuchi et al . 2007 ) and adiponectin levels ( Dastani et al . 2012 ) , neuropsychiat - ric disorders ( Franke et al . 2012 ) , and blood pressure ( Org et al . 2009 ) . A recent meta - GWAS carried out in the Afri - can populations revealed a significant association of this candidate gene with severe malaria ( Band et al . 2012 ; Man - gano and Modiano 2014 ) ."
[Show abstract][Hide abstract] ABSTRACT: The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.