Multiple distinct CHRNB3-CHRNA6 variants are genetic risk factors for nicotine dependence in African Americans and European Americans

AbstractMany studies that found associations between depression and nicotine dependence have ignored possible shared genetic influences associated with antisocial traits. The present study examined the contribution of genetic and environmental effects associated with conduct disorder (CD) and antisocial personality disorder (ASPD) to the comorbidity of major depression (MD) and nicotine dependence (ND). A telephone diagnostic interview, the Diagnostic Interview Schedule-III-R, was administered to eligible twins from the Vietnam Era Twin (VET) Registry in 1992. Multivariate genetic models were fitted to 3360 middle-aged and predominantly white twin pairs (1868 monozygotic, 1492 dizygotic pairs) of which both members completed the pertinent diagnostic interview sections. Genetic influences on CD accounted for 100%, 68%, and 50% of the total genetic variance in risk for ASPD, MD and ND, respectively. After controlling for genetic influences on CD, the partial genetic correlation between MD and ND was no longer statistically significant. Nonshared environmental contributions to the comorbidity among these disorders were not significant. This study not only demonstrates that the comorbidity between ND and MD is influenced by common genetic risk factors, but also further suggests that the common genetic risk factors overlapped with those for antisocial traits such as CD and ASPD in men.

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Interplay of genetic risk factors and parent monitoring in risk for nicotine dependence

Addiction ◽

10.1111/j.1360-0443.2009.02697.x ◽

2009 ◽

Vol 104 (10) ◽

pp. 1731-1740 ◽

Cited By ~ 32

Author(s):

Li-Shiun Chen ◽

Eric O. Johnson ◽

Naomi Breslau ◽

Dorothy Hatsukami ◽

Nancy L. Saccone ◽

...

Keyword(s):

Risk Factors ◽

Nicotine Dependence ◽

Genetic Risk ◽

Genetic Risk Factors ◽

Parent Monitoring

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202 In African Americans, NOD2, SLC22A5 and ATG16L1 But Not Il23R or IRGM Are Genetic Risk Factors for Crohn's Disease

Gastroenterology ◽

10.1016/s0016-5085(09)60173-6 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-38

Author(s):

Ming-Hsi Wang ◽

Toshihiko Okazaki ◽

Kim L. Isaacs ◽

James D. Lewis ◽

Duane T. Smoot ◽

...

Keyword(s):

Risk Factors ◽

Crohn’S Disease ◽

African Americans ◽

Crohn's Disease ◽

Genetic Risk ◽

Genetic Risk Factors

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Novel genetic predictors of venous thromboembolism risk in African Americans

Blood ◽

10.1182/blood-2015-09-668525 ◽

2016 ◽

Vol 127 (15) ◽

pp. 1923-1929 ◽

Cited By ~ 28

Author(s):

Wenndy Hernandez ◽

Eric R. Gamazon ◽

Erin Smithberger ◽

Travis J. O’Brien ◽

Arthur F. Harralson ◽

...

Keyword(s):

Gene Expression ◽

Risk Factors ◽

Venous Thromboembolism ◽

African Americans ◽

Genetic Risk ◽

Genetic Risk Factors ◽

Genetic Predictors ◽

Key Points

Key Points Our study has identified common genetic risk factors for VTE among AAs. These risk factors are associated with decreased thrombomodulin gene expression, suggesting a mechanistic link.

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P4-047 Genetic risk factors for Alzheimer's disease in African Americans

Neurobiology of Aging ◽

10.1016/s0197-4580(04)81605-1 ◽

2004 ◽

Vol 25 ◽

pp. S486

Author(s):

Mark M. Murray ◽

Robert F. Clark

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

African Americans ◽

Genetic Risk ◽

Genetic Risk Factors

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Genetic architecture of age-related cognitive decline in African Americans

Neurology Genetics ◽

10.1212/nxg.0000000000000125 ◽

2016 ◽

Vol 3 (1) ◽

pp. e125 ◽

Cited By ~ 13

Author(s):

Towfique Raj ◽

Lori B. Chibnik ◽

Cristin McCabe ◽

Andus Wong ◽

Joseph M. Replogle ◽

...

Keyword(s):

Risk Factors ◽

African Americans ◽

Cognitive Decline ◽

Genetic Risk ◽

Genetic Architecture ◽

Genetic Risk Factors ◽

Cognitive Change ◽

Age Related ◽

Age Related Cognitive Decline ◽

Shared Risk

Objective:To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs).Methods:We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS.Results:We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility.Conclusions:The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.

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Abstract P254: Genome-wide Association and Admixture Study of Iron-related Phenotypes in African Americans

Circulation ◽

10.1161/circ.129.suppl_1.p254 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Jin Li ◽

Leslie A Lange ◽

Qing Duan ◽

Monte S Willis ◽

Yun Li ◽

...

Keyword(s):

Risk Factors ◽

African Americans ◽

Iron Deficiency ◽

Genetic Risk ◽

African Ancestry ◽

Genetic Risk Factors ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Functional Variants ◽

Genome Wide

Introduction: Iron deficiency is a heritable risk factor for various serious diseases, including cardiovascular disease (CVD). Genome-wide association studies (GWAS) have identified several variants associated with iron-related phenotypes in individuals of primarily European descent. African Americans (AA) have, on average, greater levels of iron deficiency compared to European Americans, but no large-scale genetic studies for iron-related phenotypes have been performed in individuals of African ancestry to date. Methods: We conducted genome-wide admixture mapping studies and GWASs for serum iron, serum ferritin, transferrin saturation (SAT), and total binding iron capacity (TIBC) in 2347 AA participating in the Jackson Heart Study (JHS). Results: Higher proportions of estimated global African ancestry were significantly associated with lower levels of iron (p=2.4x10 -5 ), SAT (p=0.0019) and TIBC (p=0.042) and a number of chromosomal regions were observed to have local ancestry estimates nominally associated with these measures. We observed significant associations (P < 5x10 -8 ) between serum TIBC levels and multiple independent single nucleotide polymorphisms (SNPs) around TF, a well-established region for iron and transferrin levels in Caucasians, and SNPs near two novel genes: HDGFL1 and MAF. In addition, we replicated four other established loci in our AA samples including SLC17A1 , HFE , HIST1H2BJ and TMPRSS6 . Conclusions: 1) We observed SNPs in or near three genes, TF , HDGFL1 and MAF that were significantly associated with TIBC in AA. 2) We observed that both global and local genetic admixture are important predictors of iron measures in AA, further implicating the importance of certain genetic risk factors in the AA population. 3) We have also replicated four other established loci in our AA samples demonstrating the importance of some genetic risk factors for iron related measure across multiple populations. Future fine-mapping studies, incorporating less common variants, and functional studies should be undertaken to better characterize these loci and to ultimately identify the functional variants directly influencing TIBC levels in AA.

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White matter integrity and nicotine dependence in smokers: evaluating vertical and horizontal pleiotropy

10.1101/2020.12.09.417899 ◽

2020 ◽

Author(s):

Zhenyao Ye ◽

Chen Mo ◽

Kathryn Hatch ◽

Song Liu ◽

Si Gao ◽

...

Keyword(s):

Risk Factors ◽

White Matter ◽

Nicotine Dependence ◽

Genetic Risk ◽

Smoking Status ◽

Susceptibility Gene ◽

Genetic Risk Factors ◽

Cerebral White Matter ◽

Factors Associated ◽

Causal Pathway

AbstractSmoking is a heritable behavior and nicotine dependency is complex mechanism supported by both positive and negative reinforcements. We hypothesized that cerebral white matter (WM) may mediate the individual dependency on nicotine integrity because its integrity is altered in smokers and shows dose-related response to nicotine administration. Two vertical and one horizontal pleiotropy pathways that combined individual genetic variations, measure of WM integrity by fractional anisotropy (FA), and nicotine dependence were evaluated in a large epidemiological sample (N=12,264 and 4,654 participants that have genetic, FA measure and nicotine dependence data available for smoking status and cigarettes per day (CPD), respectively) collected UK Biobank. We started by selecting the candidate genetic regions including genetic risk factors associated with smoking from genome-wide association study (GWAS) for causal pathway analysis. Then we identified pleiotropic loci that influence both nicotine dependence and WM integrity from these regions. We tested a horizontal pleiotropy pathway: (A) genetic risk factors associated with smoking were independently affecting both nicotine dependence and WM integrity. We also evaluated two vertical pleiotropy that assumed that individual genetic factors associated with nicotine dependence impacted B) impacted WM integrity which in turn led to higher nicotine dependence vs. C) led to nicotine dependence and resulting white matter alterations. There were 10 and 23 candidate pleiotropic variants identified for smoking status and CPD traits. All these variants exhibited vertical pleiotropy. For smoking status, the genetic effect on smoking status was mediated by FA measures over multiple brain regions. The variants were located in a gene SARDH, which catalyzes the oxidative demethylation of sarcosine that plays a role in reducing tolerance effect on nicotine. Conversely, CPD was a significant mediator in the vertical pleiotropy pathway to FA. The identified variants were located in gene IREB2, that was reported as a susceptibility gene for both neurodegeneration and smoking-induced diseases.

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