Heritability, SNP- and Gene-Based Analyses of Cannabis Use Initiation and Age at OnsetReport as inadecuate




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Behavior Genetics

, Volume 45, Issue 5, pp 503–513

First Online: 19 May 2015Received: 05 November 2014Accepted: 27 April 2015DOI: 10.1007-s10519-015-9723-9

Cite this article as: Minică, C.C., Dolan, C.V., Hottenga, JJ. et al. Behav Genet 2015 45: 503. doi:10.1007-s10519-015-9723-9

Abstract

Prior searches for genetic variants GVs implicated in initiation of cannabis use have been limited to common single nucleotide polymorphisms SNPs typed in HapMap samples. Denser SNPs are now available with the completion of the 1000 Genomes and the Genome of the Netherlands projects. More densely distributed SNPs are expected to track the causal variants better. Therefore we extend the search for variants implicated in early stages of cannabis use to previously untagged common and low-frequency variants. We run heritability, SNP and gene-based analyses of initiation and age at onset. This is the first genome-wide study of age at onset to date. Using GCTA and a sample of distantly related individuals from the Netherlands Twin Register, we estimated that the currently measured and tagged SNPs collectively explain 25 % of the variance in initiation SE = 0.088; P = 0.0016. Chromosomes 4 and 18, previously linked with cannabis use and other addiction phenotypes, account for the largest amount of variance in initiation 6.8 %, SE = 0.025, P = 0.002 and 3.6 %, SE = 0.01, P = 0.012, respectively. No individual SNP- or gene-based test reached genomewide significance in the initiation or age at onset analyses. Our study detected association signal in the currently measured SNPs. A comparison with prior SNP-heritability estimates suggests that at least part of the signal is likely coming from previously untyped common and low frequency variants. Our results do not rule out the contribution of rare variants of larger effect—a plausible source of the difference between the twin-based heritability estimate and that from GCTA. The causal variants are likely of very small effect i.e., <1 % explained variance and are uniformly distributed over the genome in proportion to chromosomes’ length. Similar to other complex traits and diseases, detecting such small effects is to be expected in sufficiently large samples.

KeywordsCannabis Initiation Age at onset Heritability Edited by Sarah Medland.

Electronic supplementary materialThe online version of this article doi:10.1007-s10519-015-9723-9 contains supplementary material, which is available to authorized users.

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Author: Camelia C. Minică - Conor V. Dolan - Jouke-Jan Hottenga - René Pool - The Genome of the Netherlands Consortium - Iryna O.

Source: https://link.springer.com/







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