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- Li, Chen, et al.
(författare)
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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
- 2020
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Ingår i: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 106:3, s. 389-404
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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| 2. |
- Kendler, Kenneth S., et al.
(författare)
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Does neighborhood alcohol availability moderate the impact of familial liability and marital status on risk for alcohol use disorders? A Swedish national study
- 2020
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Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 81:6, s. 816-823
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this study was to determine whether ease of access to alcohol at the neighborhood level moderates the impact of familial liability and marital status on risk for alcohol use disorder (AUD). Method: Individuals in Sweden were divided into those residing in a neighborhood with (n = 14.1%) versus without (n = 85.9%) an alcohol outlet (bars/nightclubs or government stores). AUD was detected through national medical, legal, and pharmacy registries. Using an additive model predicting AUD registration over 5 years in 1,624,814 individuals, we tested for interactions between the presence of outlets in the individuals’ neighborhoods and familial risk for external-izing syndromes and marital status. Results: In both males and females, we found positive and significant interactions in the prediction of AUD between the presence versus absence of a nearby alcohol outlet with (a) familial risk and (b) single and divorced versus married status. Similar but nonsignificant interactions were seen between nearby outlets and widowed versus married status. These results changed little when all cases with prior AUD were removed from the sample. For males, most of the interaction arose from the proximity of bars/nightclubs, whereas for females the results varied across different kinds of outlets. Conclusions: Environments that provide easy access to alcohol augment the impact of a range of risk factors for AUD, especially familial vulnerability and the reduced social constraints associated with single, divorced, and widowed marital status.
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| 3. |
- Salvatore, Jessica E., et al.
(författare)
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Disentangling Social-Genetic From Rearing-Environment Effects for Alcohol Use Disorder Using Swedish National Data
- 2020
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Ingår i: Psychological Science. - : SAGE Publications. - 0956-7976 .- 1467-9280. ; 31:9, s. 1140-1149
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Tidskriftsartikel (refereegranskat)abstract
- Investigations of social-genetic effects, whereby a social partner’s genotype affects another’s outcomes, can be confounded by the influence of the social partner’s rearing environment. We used marital information on more than 300,000 couples from Swedish national data to disentangle social-genetic from rearing-environment effects for alcohol use disorder (AUD). Using observational and extended-family designs, we found that (a) marriage to a spouse with a predisposition toward AUD (as indexed by a parental history of AUD) increased risk for developing AUD; (b) this increased risk was not explained by socioeconomic status, the spouse’s AUD status, or contact with the spouse’s parents; and (c) this increased risk reflected the psychological consequences of the spouse having grown up with an AUD-affected parent (i.e., a rearing-environment effect) rather than a social-genetic effect. Findings illustrate that a spouse’s rearing-environment exposures may confer risk for AUD.
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