rs11118303 LYPLAL1-AS1 expression in adrenal gland

What the research says rs11118303 is located in the LYPLAL1-AS1 gene region - a long non-coding antisense RNA, meaning it is transcribed from DNA but does not directly encode a protein - and was identified in a genome-wide association study (GWAS, a large scan of the entire genome to find variants linked to measurable traits) of allometric body-shape indices conducted in the UK Biobank, analyzing 219,872 women and 186,825 men of white British ancestry using Bayesian linear mixed-models (BOLT-LMM) [Study 1]. The study examined three body-shape measures adjusted for both BMI (body mass index) and height: A Body Shape Index (ABSI, capturing central abdominal shape), Hip Index (HI), and a Waist-to-Hip Index (WHI), with the stated goal of removing the confounding influence of height that affects traditional waist and hip measures [Study 1]. The study reported that one to two thirds of the genomic loci (distinct chromosomal regions) it identified were novel, with highly ranked genes including those previously linked to morphogenesis (the biological process governing body shape development) and organogenesis (organ formation) [Study 1].

Reported associations

• Allometric body-shape indices: Identified in a GWAS of body-shape measures independently adjusted for both BMI and height (ABSI, HI, and WHI) across a large population cohort [Study 1]
• Sex-differentiated genetic architecture: The study found fewer genetic associations with body-shape indices in men than in women, consistent with known sexual dimorphism (biological sex differences) in fat distribution genetics [Study 1]

Evidence quality The study's primary strength is its large sample size - over 400,000 UK Biobank participants - which provides substantial statistical power to detect genetic associations [Study 1]. The study was restricted to individuals of white British ancestry, which is an important limitation: findings may not generalize to individuals of other ancestries [Study 1]. The authors described this as the first GWAS of allometric body-shape indices, meaning independent replication of these specific loci in external cohorts had not yet been reported at the time of the study [Study 1]. The specific p-value and effect size for rs11118303 are not reported in the text excerpt provided. No conflicting studies were provided for this variant.

Tissue-specific expression effects

• LYPLAL1-AS1: The alternate allele of rs11118303 is associated with substantially reduced expression of LYPLAL1-AS1 in the adrenal gland (a hormone-producing gland situated above each kidney), with a large effect size and very strong statistical confidence (p=3.2×10^-²^0) [GTEx]. The same allele is associated with modestly increased LYPLAL1-AS1 expression in two skin tissue types: non-sun-exposed skin (suprapubic region, p=1.2×10^-5) and sun-exposed skin (lower leg, p=1.4×10^-4) [GTEx]. These are eQTL effects - the variant changes how much the gene is read in specific tissues - and do not on their own establish functional or clinical consequences.

Study sources

1. Unknown authors, Unknown journal, year unknown - GWAS of allometric body-shape indices (ABSI, HI, WHI) in UK Biobank; traits: body shape and fat distribution