Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use

Marees, Andries T.; Bastarache, Lisa; Kluiver, Hilde de; Vorspan, Florence; Brink, Wim van den; Smit, Dirk J.A.; Denys, Damiaan; Gamazon, Eric R.; Li‐Gao, Ruifang; Breetvelt, Elemi J.; Groot, Mark de; Galesloot, Tessel E.; Vermeulen, Sita H.; Poppelaars, Jan; Souverein, Patrick C.; Keeman, Renske; Mutsert, Renée de; Noordam, Raymond; Rosendaal, Frits R.; Stringa, Najada; Mook‐Kanamori, Dennis O.; Vaartjes, Ilonca; Kiemeney, Lambertus A.; Heijer, Martin den; Schoor, Natasja M. van; Klungel, Olaf H.; Zee, Anke‐Hilse Maitland‐van der; Schmidt, Marjanka K.; Polderman, Tinca J. C.; Leij, Andries R. van der; Posthuma, Daniëlle; Derks, Eske M.

doi:10.1016/j.drugalcdep.2018.03.026

Cited by 14 publications

(12 citation statements)

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“…The missense mutation rs16969968 (RefSeqGene NG_023328.1:g.30064G>A), a frequent SNV (called single nucleotide polymorphism (SNP)), changing one amino acid in the α5 protein at position 398, from aspartate to asparagine, has been the focus of extensive clinical and preclinical research due to robust and repeated evidence for association of its risk allele (A in populations with Caucasian ancestry) with NA. rs16969968 has been repeatedly associated with NA, including in a first GWAS in 2008 (Thorgeirsson et al, 2008), an observation further strengthened by meta-analyses (Liu et al, 2010;Marees et al, 2018). The presence of this SNP doubles the risk to develop NA for AA compared to GG genotypes (Saccone et al, 2007).…”

Section: Genetic Associations Between Chrna5 and Namentioning

confidence: 86%

Genetic susceptibility to nicotine addiction: Advances and shortcomings in our understanding of the CHRNA5/A3/B4 gene cluster contribution

et al. 2020

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Section: Genetic Associations Between Chrna5 and Namentioning

confidence: 86%

Genetic susceptibility to nicotine addiction: Advances and shortcomings in our understanding of the CHRNA5/A3/B4 gene cluster contribution

et al. 2020

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“…Previously, several analyses of smoking‐related phenotypes using the Exome chip revealed multiple common and rare susceptibility loci, such as variants in REV3L , CNNM2 , CHRNA5 , and AGPHD1 , 63–65 in single SNP analysis. However, the identification of causal genes through gene‐based analysis with rare variants barely achieved the defined p value threshold for significance.…”

Section: Discussionmentioning

confidence: 99%

Gene‐based association analysis reveals involvement of LAMA5 and cell adhesion pathways in nicotine dependence in African‐ and European‐American samples

et al. 2020

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Nicotine dependence (ND) is a chronic brain disorder that causes heavy social and economic burdens. Although many susceptibility genetic loci have been reported, they can explain only approximately 5%–10% of the genetic variance for the disease. To further explore the genetic etiology of ND, we genotyped 242 764 SNPs using an exome chip from both European‐American (N = 1572) and African‐American (N = 3371) samples. Gene‐based association analysis revealed 29 genes associated significantly with ND. Of the genes in the AA sample, six (i.e., PKD1L2, LAMA5, MUC16, MROH5, ATP8B1, and FREM1) were replicated in the EA sample with p values ranging from 0.0031 to 0.0346. Subsequently, gene enrichment analysis revealed that cell adhesion‐related pathways were significantly associated with ND in both the AA and EA samples. Considering that LAMA5 is the most significant gene in cell adhesion‐related pathways, we did in vitro functional analysis of this gene, which showed that nicotine significantly suppressed its mRNA expression in HEK293T cells (p < 0.001). Further, our cell migration experiment showed that the migration rate was significantly different in wild‐type and LAMA5‐knockout (LAMA5‐KO)‐HEK293T cells. Importantly, nicotine‐induced cell migration was abolished in LAMA5‐KO cells. Taken together, these findings indicate that LAMA5, as well as cell adhesion‐related pathways, play an important role in the etiology of smoking addiction, which warrants further investigation.

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“…Exome chip data and a number of SNPs in candidate genes are available for a subsample of respondents in the first cohort (n = 1193) (see for example [20]). Furthermore, genotyping of Apolipoprotein E gene is also available for a subset of respondents in the second cohort (n = 753).…”

Section: Genetic Datamentioning

confidence: 99%

The Longitudinal Aging Study Amsterdam: cohort update 2019 and additional data collections

et al. 2019

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The Longitudinal Aging Study Amsterdam (LASA) is a prospective cohort study of older adults in the Netherlands, initially based on a nationally representative sample of people aged 55-84 years. The study has been ongoing since 1992, and focuses on the determinants, trajectories and consequences of physical, cognitive, emotional and social functioning. Strengths of the LASA study include its multidisciplinary character, the availability of over 25 years of follow-up, and the cohort-sequential design that allows investigations of longitudinal changes, cohort differences and time trends in functioning. The findings from LASA have been reported in over 600 publications so far (see www.lasa-vu.nl). This article provides an update of the design of the LASA study and its methods, on the basis of recent developments. We describe additional data collections, such as additional nine-monthly measurements in-between the regular three-yearly waves that have been conducted among the oldest old during 2016-2019, and the inclusion of a cohort of older Turkish and Moroccan migrants.

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Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use

Cited by 14 publications

References 68 publications

Genetic susceptibility to nicotine addiction: Advances and shortcomings in our understanding of the CHRNA5/A3/B4 gene cluster contribution

Genetic susceptibility to nicotine addiction: Advances and shortcomings in our understanding of the CHRNA5/A3/B4 gene cluster contribution

Gene‐based association analysis reveals involvement of LAMA5 and cell adhesion pathways in nicotine dependence in African‐ and European‐American samples

The Longitudinal Aging Study Amsterdam: cohort update 2019 and additional data collections

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