Extended Data Fig. 5. Allele effects characterize genome-lipid hotspots.

a, Hierarchical clustering of allele effects at Chr 6:91 Mbp resulted in 21 features with matching A/J down effect (main cluster featuring the six B6 male specific features (red) after row-scaling and Ward clustering, cutoff at h=5). b, Consistently, the pattern of male >> female was observed for each of the FS except for A/J as visible in the example for m/z 1130 (n = 4 for each sex and strain, boxplots are defined with the first and third quartiles (25th and 75th percentile) for lower and upper hinges, 1.5x interquartile range for the length of the whiskers, center line at median (50% quantile).) c, Hierarchical clustering of allele effects at Chr 5:31 Mbp locus resulted in 10 features with matching B6 and NZO up effect (main cluster featuring LysoPC 14:0 (turquoise) after row-scaling and Ward clustering, cutoff at h=8). d, This pattern could be replicated in the FS (n = 4 for each sex and strain, boxplots are defined with the first and third quartiles (25th and 75th percentile) for lower and upper hinges, 1.5x interquartile range for the length of the whiskers, center line at median (50% quantile)), as shown for LysoPC 14:0, as well as e, in opposite directionality in a liver eQTL.³⁴ f, Hierarchical clustering of allele effects at Chr 7:79 Mbp locus resulted in 8 features with matching WSB down effect (main cluster featuring PUFA-containing phospholipids (turquoise) after row-scaling and Ward clustering, cutoff at h=2.5). g, The mapping phospholipids contained polyunsaturated fatty acids such as 20:4 and 22:6. h-i, Abhd2 liver RNA and protein allele effects³⁴ matched with an opposite WSB high effect. Abbreviations: DO (diversity outbred), FS (founder strain), Chr (chromosome), Mbp (megabase pair), PC (phosphatidylcholine), PUFA (polyunsaturated fatty acid).