In:
Alcoholism: Clinical and Experimental Research, Wiley, Vol. 42, No. 3 ( 2018-03), p. 520-530
Abstract:
Despite consistent evidence of the heritability of alcohol use disorders ( AUD s), few specific genes with an etiological role have been identified. It is likely that AUD s are highly polygenic; however, the etiological pathways and genetic variants involved may differ between populations. The aim of this study was thus to evaluate whether aggregate genetic risk for AUD s differed between clinically ascertained and population‐based epidemiological samples. Methods Four independent samples were obtained: 2 from unselected birth cohorts (Avon Longitudinal Study of Parents and Children [ ALSPAC ], N = 4,304; FinnTwin12 [FT12], N = 1,135) and 2 from families densely affected with AUD s, identified from treatment‐seeking patients (Collaborative Study on the Genetics of Alcoholism, N = 2,097; Irish Affected Sib Pair Study of Alcohol Dependence, N = 706). AUD symptoms were assessed with clinical interviews, and participants of European ancestry were genotyped. Genomewide association was conducted separately in each sample, and the resulting association weights were used to create polygenic risk scores in each of the other samples (12 total discovery–validation pairs), and from meta‐analyses within sample type. We then tested how well these aggregate genetic scores predicted AUD outcomes within and across sample types. Results Polygenic scores derived from 1 population‐based sample ( ALSPAC ) significantly predicted AUD symptoms in another population‐based sample (FT12), but not in either clinically ascertained sample. Trend‐level associations (uncorrected p 〈 0.05) were found for polygenic score predictions within sample types but no or negative predictions across sample types. Polygenic scores accounted for 0 to 1% of the variance in AUD symptoms. Conclusions Though preliminary, these results provide suggestive evidence of differences in the genetic etiology of AUD s based on sample characteristics such as treatment‐seeking status, which may index other important clinical or demographic factors that moderate genetic influences. Although the variance accounted for by genomewide polygenic scores remains low, future studies could improve gene identification efforts by amassing very large samples, or reducing genetic heterogeneity by informing analyses with other phenotypic information such as sample characteristics. Multiple complementary approaches may be needed to make progress in gene identification for this complex disorder.
Type of Medium:
Online Resource
ISSN:
0145-6008
,
1530-0277
DOI:
10.1111/acer.2018.42.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2046886-6
detail.hit.zdb_id:
3167872-5
SSG:
15,3
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