Genome-wide association summary statistics for plasma Lp(a) in the UK Biobank

This dataset contains the genome-wide association summary statistics for plasma Lp(a) performed on the UK Biobank White British individuals. For more details, see Hoekstra et al., Genome-Wide Association Study Highlights APOH as a Novel Locus for Lipoprotein(a) Levels-Brief Report, Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):458-464. doi: 10.1161/ATVBAHA.120.314965. Epub 2020 Oct 29.

The data are provided on an "AS-IS" basis, without warranty of any type, expressed or implied, including but not limited to any warranty as to their performance, merchantability, or fitness for any particular purpose. If investigators use these data, any and all consequences are entirely their responsibility. By downloading and using these data, you agree that you will cite the appropriate publication in any communications or publications arising directly or indirectly from these data. This research has been conducted using the UK Biobank Resource application # 41025.

Objective: Lipoprotein(a) (Lp(a)) is an independent risk factor for cardiovascular diseases and plasma levels are primarily determined by variation at the LPA locus. We performed a genome-wide association study (GWAS) in the UK Biobank to determine whether additional loci influence
Lp(a) levels.

Approach and Results: We included 293,274 White British individuals in the discovery analysis. Approximately 93,095,623 variants were tested for association with natural log- transformed Lp(a) levels using linear regression models adjusted for age, sex, genotype batch, and 20 principal components of genetic ancestry. After quality control, 131 independent variants were associated at genome-wide significance (P ≤ 5 × 10⁻⁸ ). In addition to validating previous associations at LPA , APOE , and CETP , we identified a novel variant at the APOH locus, encoding beta2-glycoprotein I (β2GPI). The APOH variant rs8178824 was associated with increased Lp(a) levels (β [95% CI] (ln nmol/L), 0.064 [0.047, 0.081]; P = 2.8 × 10⁻¹³ ) and demonstrated a stronger effect after adjustment for variation at the LPA locus (β [95% CI] (ln nmol/L), 0.089 [0.076, 0.10]; P = 3.8 × 10⁻⁴² ). This association was replicated in a meta-analysis of 5,465 European-ancestry individuals from the Framingham Offspring Study and Multi-Ethnic Study of Atherosclerosis (β [95% CI] (ln mg/dL), 0.16 [0.044, 0.28]; P = 0.0071).

Conclusions: In a large-scale GWAS of Lp(a) levels, we identified APOH as a novel locus for Lp(a) in individuals of European ancestry. Additional studies are needed to determine the precise role of β2GPI in influencing Lp(a) levels as well as its potential as a therapeutic target.

When using this data, please cite the paper and this repository:

1. Hoekstra et al., Genome-Wide Association Study Highlights APOH as a Novel Locus for Lipoprotein(a) Levels-Brief Report, Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):458-464. doi: 10.1161/ATVBAHA.120.314965. Epub 2020 Oct 29.

2. Zenodo. 10.5281/zenodo.7554928

Funding

Funding for this study was obtained from NIH, CIHR and HSFC.

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OTHER_ALLELE
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