Table 1 Putative novel variants identified in TOPMed and evidence for replication

From: Whole genome sequence analysis of blood lipid levels in >66,000 individuals

Associated lipid phenotype

Novel variant class

Variants (Gene)

Discovery Cohort TOPMed Freeze8 (N = 66,329)

Replication Cohort Meta Analysis (METASOFT) MGB Biobank (N = 25,137); Penn Medicine Biobank (N = 20,079); UK Biobank (N = 424,955)

Effect estimate

p-value

MAF

Beta

p-value

Std.Err

LDL-C

Novel locus

12:97352354:T:C

−12.439

4.88 × 10−09

0.003

3.316

3.62 x 10−01

3.634

LDL-C

Novel variant

16:56957451:C:T (CETP)

−1.568

2.88 × 10−09

0.283

−1.459

8.74 x 10−84

0.075

LDL-C

Novel locus

4:176382171:C:T

−16.086

2.82 × 10−09

0.002

−0.980

7.80 x 10−01

3.514

TC

Novel variant

13:113841051:T:C (GAS6)

1.731

1.12 × 10−09

0.278

1.262

1.29 x 10−38

0.097

TC

Novel variant

7:137875053:T:C (CREB3L2)

−4.106

7.54 × 10−11

0.045

−3.538

7.70 x 10−07

0.716

TG

Novel locus

11:69219641:C:T

0.232

1.98 × 10−09

0.002

−0.030

6.04 x 10−01

0.059

TG

Novel variant

13:107551611:C:T (FAM155A)

0.052

6.78 × 10−10

0.045

0.015

2.20 x 10−02

0.006

  1. Variants identified as novel after comparing with the GWAS catalog and MVP summary statistics for associations with lipid phenotypes, including LDL-C, TC, and TG. All effect estimates are in mg/dL units, except for TG which was log-transformed in analysis thereby representing fractional change. Variants are categorized as novel loci or novel variant (i.e., known locus associated with another lipid phenotype) and the genes assigned to the variants per TOPMed whole genome sequence annotations (WGSA) are listed. Data is provided for the discovery (TOPMed freeze8) and replication cohorts (Imputed datasets from MGB Biobank, Penn Medicine Biobank and UK Biobank). Meta-analysis with the replication cohorts was carried out and the corresponding beta, p-values and standard-errors are provided. All the effect-estimates and p-values are reported from two-sided association testing with all independent samples from each cohort (Discovery-TOPMed: 66,329; Replication-MGB Biobank: 25,137; UK Biobank: 424,955; Penn Biobank: 20,079).
  2. GWAS genome wide association study, MVP million veteran program, LDL-C low-density lipoprotein cholesterol, TC total cholesterol, TG triglycerides, TOPMed trans-omics for precision medicine, WGSA whole genome sequence annotations.
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